RxPG News : AIDS

U of M scientist gets 5-year, $10 million grant to direct innovative HIV research program

Mon, 18 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Reuben Harris, professor in the University of Minnesota's College of Biological Sciences, has been awarded a five-year, $10 million grant from the National Institutes of Health to direct a large-scale research effort to study a human antiviral protein with potential for treating HIV and other viral diseases.

The goal of the study will be to produce atomic resolution images of the protein (APOBEC3G) to better understand how it interacts with other proteins in human cells and with HIV to prevent the virus from attaching to and entering cells. This fundamental knowledge could lead to novel methods to alter this protein to make it more effective.

You have to understand the nuts and bolts of the system before you can make alterations to interfere with the process, says Harris, an associate professor of biochemistry, molecular biology and biophysics. I'm very optimistic that this will research will enable us to use this novel protein against HIV and other diseases.

The approach represents a paradigm shift in treating viral diseases. While most other strategies focus on the virus itself, this is among the first to focus on the host.

Conventional methods focusing on HIV are susceptible to the inevitable emergence of drug resistant virus isolates, whereas drugs that target stable cellular proteins may be much less prone to this problem says Harris.

Human cells produce a family of antiviral proteins (called APOBECs) that have the ability to destroy HIV. But HIV has evolved a way to overcome them using an accessory protein called Vif (virion infectivity factor) to degrade the APOBEC proteins and allow the virus to spread. In a previous study, researchers in Harris's lab showed how HIV binds to and destroys one of the APOBEC proteins. This suggests that a simple change in the chemical structure of the APOBEC proteins could convert the human proteins to more effective antiviral agents. A better understanding of the interaction at molecular and atomic levels is needed to move in that direction.

Harris will lead five teams with complementary skills in molecular virology, NMR spectroscopy, X-ray crystallography, biophysics and biochemistry. Matsuo Hiroshi, associate professor in the College of Biological Sciences, is also a project leader, and Joachim Mueller, associate professor in the College of Science and Engineering's Department of Physics, is a key interdepartmental collaborator. Other sites include the University of Massachusetts Medical School, University of Nebraska and Hebrew University in Israel. Funded by the National Institute of General Medical Sciences, this Program Project grant will support training opportunities for students while advancing research. About half of the projected full amount of the $10 million grant will remain at the University of Minnesota.

New drug regimens cut HIV spread from mother to infant

Wed, 02 Mar 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Pregnant women who are unaware that they have HIV miss the chance for drug treatment that can benefit not only their own health, but could also prevent them from transmitting the virus to their infants. When HIV is not diagnosed until women go into labor, their infants are usually treated soon after birth with the anti HIV drug zidovudine (ZDV), to prevent the infants from becoming infected with the virus.

Now, a National Institutes of Health study has found that adding one or two drugs to the standard ZDV treatment can reduce the chances by more than 50 percent that an infant will develop an HIV infection.

The study results were presented on, March 2, at the 18th Conference on Retroviruses and Opportunistic Infections, in Boston. The study was conducted at research hospitals in Brazil, South Africa, Argentina, and the United States, under contract to the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Additional funding was provided by the NIH's National Institute of Allergy and Infectious Diseases.

An estimated one fifth of people in the United States who have HIV are unaware that they harbor the virus. From 100 to 200 infants are born with HIV in the United States each year, many to women who either were not tested in early pregnancy or who did not receive treatment during pregnancy. Internationally, estimates of HIV testing vary, with only 21 percent of pregnant women in low and middle income countries having been tested for HIV during pregnancy.

To reduce mother-to-child HIV transmission, it's best to begin antiretroviral treatment during pregnancy, said Heather Watts, M.D., a medical officer in NICHD's Pediatric, Adolescent and Maternal AIDS Branch, and an author of the study. However, when treatment during pregnancy isn't possible, our results show that adding one or two drugs to the current regimen provides another important means to reduce the chance for mother-to-child HIV transmission.

At the 19 participating research sites, the NICHD/ HIV Prevention Trials Network 040 study evaluated 1,684 infants born to women whose HIV infections were not diagnosed until they were in labor. The infants were randomly assigned to three groups: those receiving the standard 6 weeks of therapy with ZDV, those receiving 6 weeks of ZDV plus 3 doses of nevirapine (NVP) during the first week of life, and those receiving 6 weeks of ZDV plus two weeks of lamivudine (3TC) and nelfinavir (NFV). The study results showed that treatment with the two and three drug regimens reduced HIV transmission by more than 50 percent.

ZDV, ZDV+NVP, ZDV+3TC+NFV

6-month drug regimen cuts HIV risk for breastfeeding infants, NIH study finds

Wed, 02 Mar 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Giving breastfeeding infants of HIV-infected mothers a daily dose of the antiretroviral drug nevirapine for six months halved the risk of HIV transmission to the infants at age 6 months compared with giving infants the drug daily for six weeks, according to preliminary clinical trial data presented today.

The longer nevirapine regimen achieved a 75 percent reduction in HIV transmission risk through breast milk for the infants of HIV-infected mothers with higher T-cell counts who had not yet begun treatment for HIV.

The study was presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

Extended breastfeeding reduces infant mortality in places that lack safe, clean water by protecting babies from common childhood diseases because breast milk contains protective antibodies from the mother that formula feeding does not provide, says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, which funds the trial. These findings show that giving the infants of HIV-infected mothers an antiretroviral drug daily for the full duration of breastfeeding safely minimizes the threat of HIV transmission through breast milk while preserving the health benefits of extended breastfeeding.

The new findings apply to mothers and infants in developing nations, where infectious diseases such as gastroenteritis and pneumonia often pose a life-threatening risk to very young children. The U.S. Department of Health and Human Services recommends that HIV-infected mothers in the United States feed their babies with infant formula, not breast milk, because safe and affordable formula is available, infant deaths due to infections are low and only total avoidance of breastfeeding will completely protect these infants from HIV transmission through breast milk.

This advanced-stage clinical trial known as HPTN 046 is co-funded by NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Drug Abuse and the National Institute of Mental Health, all part of NIH. The HIV Prevention Trials Network and the International Maternal, Pediatric and Adolescent AIDS Clinical Trials Network are conducting the trial under the leadership of Hoosen Coovadia, M.D., M.B.B.S., of the University of the Witwatersrand in Durban, South Africa. Bonnie Maldonado, M.D., of Stanford University in Stanford, Calif., presented the study results for Dr. Coovadia on March 2, 2011, at CROI.

More than 1,500 mother-infant pairs in South Africa, Tanzania, Uganda and Zimbabwe are participating in HPTN 046, which began in February 2007 and will conclude in July 2011. The participating infants received daily nevirapine for the first six weeks after birth. Those infants who remained free of HIV then were assigned at random to receive either daily nevirapine or a placebo until six months after birth or the cessation of breastfeeding, whichever came first. Study investigators compared the rates of HIV infection in the two groups of infants, and evaluated and compared the safety and tolerance of nevirapine in the infants.

New vaccine technology protects mice from hepatitis C virus

Wed, 23 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Immunology: Three percent of the world's population is currently infected by hepatitis C. The virus hides in the liver and can cause cirrhosis and liver cancer, and it's the most frequent cause of liver transplants in Denmark. Since the virus mutates strongly, we have no traditional vaccine, but researchers at the University of Copenhagen are now the first to succeed in developing a vaccine, which provides future hope for medical protection from this type of hepatitis.

The hepatitis C virus (HCV) has the same infection pathways as HIV, says Jan Pravsgaard Christensen, Associate Professor of Infection Immunology at the Faculty of Health Sciences, University of Copenhagen.

Approximately one newly infected patient in five has an immune system capable of defeating an acute HCV infection in the first six months. But most cases do not present any symptoms at all and the virus becomes a chronic infection of the liver.

Poorly treated donor blood and dirty needles are sinners

Every year three or four million more people become infected and the most frequent path of infection is needle sharing among drug addicts or tattoo artists with poor hygiene, such as tribal tattoo artists in Africa and Asia. Fifteen percent of new infections are sexually transmitted, while ten percent come from unscreened blood transfusions.

According to Allan Randrup Thomsen, Professor of Experimental Virology, Egypt is one country with a high incidence of HCV. This is particularly due to lack of caution in the past with regards to screening donated blood for the presence of this virus, he says.

China, Brazil, South East Asia and African states south of the Sahara also have a high incidence, while the disease is also spreading through Eastern Europe, especially Romania and Moldova.

HCV mutates too fast for traditional vaccines

The new vaccine technology was developed by Peter J. Holst, a former PhD student now a postdoc with the Experimental Virology group, which also includes Professor Allan Randrup Thomsen and Associate Professor Jan Pravsgaard Christensen.

The technology works by stimulating and accelerating the immune system, and showing the body's defence mechanisms of the parts of the virus that are more conserved and do not mutate as fast and as often, such as the molecules on the surface of the HCV.

Basically, traditional vaccines work by showing the immune defences an identikit image of the virus for which protection is desired. Antibodies then patrol all entrances with a copy of this image and are able to respond rapidly if the virus attempts to penetrate. But the influenza virus mutates its surface molecules and in the course of a single season it takes on a new guise so that it no longer resembles the original identikit image and the vaccine loses its efficacy.

Professor Randrup explains, Mutations of the surface are Darwin at work, so to speak. The virus tries to outwit the immune defences and if it succeeds we get ill, and our response is new vaccines.

Associate Professor Pravsgaard Christensen says, Viruses like HCV mutate so rapidly that classical vaccine technology hasn't a chance of keeping up. But the molecules inside the virus do not mutate that rapidly, because the survival of the virus does not depend on it.

New vaccine technology gives immune system information about virus' stable parts

According to Professor Randrup, the body's natural defences usually don't see these internal virus molecules until the virus has taken residence in the body.

Our cells constantly show random samples of their contents to the immune defence patrols, and if there are enough foreign bodies among them, the alarm is triggered, says Professor Randrup.

The cells display fragments of the surface molecules and internal genes from the virus, and if you show the immune defences a kind of X-ray of the inner genes, they will respond. Actually, the response is extremely potent, and one of the things it does is summon the specialised CD8 killer cells.

We took a dead common cold virus, an adenovirus that is completely harmless and which many of us have met in childhood, Associate Professor Pravsgaard Christensen explains.

We hid the gene for one of the HCV's internal molecules inside it. At the same time we attached a special molecule on the internal molecule so that when the cells of the mouse body tried to take a sample, they would extract a more extensive section. The immune defences would then be presented with a larger section of the molecule concerned. You may say that the immune defences were given an entire palm print of the internal genes instead of just a single fingerprint.

This strategy resulted in two discoveries from the team. Firstly, the mice were vaccinated for HCV in a way that meant that protection was independent of variations in the surface molecules of the virus. Secondly, the immune defences of the mice saw such an extensive section of the internal molecule that even though some aspects of it changed, there were still a couple of impressions the immune defences could recognise and respond to.

The new technology to be tested in monkeys

Another virus that mutates its surface molecules with extreme rapidity is HIV. It changes skin in the space of 24 hours, and like HCV, we do not yet have a cure or a vaccine. The researchers think that HIV originally migrated to man from monkeys in the 1930s, when it was the simian Immunodeficiency virus that still circulates among a number of species of wild African monkeys.

The Danish Medical Research Council (DMRC) has given postdoc Peter Holst a grant to test our technology for a SIV vaccine for macaque monkeys in the US, says Associate Professor Pravsgaard Christensen.

The University of Copenhagen is also currently negotiating the sale of the patent for the process so that the technology can be developed for use in human vaccines.

The discovery of an effective HCV vaccine has just been published in the

Study suggests why HIV-uninfected babies of mothers with HIV might be more prone to infections

Tue, 08 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Babies whose mothers have HIV, but who are not HIV-infected themselves, are born with lower levels of specific proteins in their blood called antibodies, which fight infection, compared with babies not exposed to HIV, a new study has found. The finding, published today in the Journal of the American Medical Association, might explain in part why uninfected babies born to women with HIV have a higher risk of illness and death early in life.

Major programmes using antiretroviral drugs have successfully reduced the rate of mother-to-child transmission of HIV from 20-30 per cent to around five per cent in some areas of South Africa and to less than one per cent in developed countries. However, HIV-uninfected infants born to HIV-infected mothers in Africa are more prone to infections such as pneumonia and meningitis, and up to four times more likely to die before their first birthday, compared with babies born to HIV-negative women. Socioeconomic factors are thought to account partially for this discrepancy but differences in the babies' immune systems might also be important.

The new study, by scientists from Imperial College London and Stellenbosch University in South Africa, found that babies born to HIV-infected mothers had significantly lower levels at birth of antibodies against a range of bacterial infections (Hib, pertussis, pneumococcus and tetanus).

Antibodies, which bind to specific pathogens and direct immune cells to attack them, are transferred from mother to child through the placenta late in pregnancy. The study found lower levels of some specific antibodies in mothers with HIV, but also that less antibody is transferred from mother to child across the placenta.

Despite their low antibody levels at birth, the babies in the study responded well to vaccination: they produced similar levels of antibody to some vaccines and higher levels to other vaccines.

It's likely that lower antibody levels in these babies contributes to lower protection against infection before the babies have received their vaccines, said Dr Christine Jones from the Department of Paediatrics at Imperial College London, the study's first author. Although they appear more vulnerable in the first few months of life, the good news is that these babies respond well to vaccination. We might be able to protect them even better against infections, either by vaccinating them earlier or by vaccinating the mother in pregnancy. More research will be needed to establish what the best way of protecting these babies might be.

The study involved 109 HIV-infected and uninfected mothers in a community health centre in Khayelitsha, a rapidly-growing township in Cape Town, South Africa. The researchers measured antibody levels in the mothers at delivery and the infants at birth. They also assessed how the babies responded to routine vaccination by measuring the babies' antibody levels at four months, after they had received their routine vaccines.

Amongst the HIV-negative women in the study, a third also had low antibody levels, showing that protection against infection in their babies might also not be optimal in some women, who are otherwise perfectly healthy.

Broadly-reactive neutralizing antibodies bring scientists closer to HIV vaccine

Thu, 13 Jan 2011 18:42:29 PST

( from http://www.rxpgnews.com ) New findings are bringing scientists closer to an effective HIV vaccine. Researchers from Seattle Biomedical Research Institute (Seattle BioMed), Vanderbilt University and the Ragon Institute of MGH, MIT and Harvard report findings showing new evidence about broadly-reactive neutralizing antibodies, which block HIV infection. Details are published January 13 in the open-access journal PLoS Pathogens.
According to author Leo Stamatatos, Ph.D., director of the Viral Vaccines Program at Seattle BioMed and a major stumbling block in the development of an effective vaccine against HIV is the inability to elicit, by immunization, broadly reactive neutralizing antibodies (NAbs). These antibodies bind to the surface of HIV and prevent it from attaching itself to a cell and infecting it. However, a fraction of people infected with HIV develop broadly neutralizing antibodies (bNAbs) capable of preventing cell-infection by diverse HIV isolates, which are the type of antibodies researchers wish to elicit by vaccination.
"We've found that the people who develop broadly-reactive neutralizing antibodies - which are about 30% of those infected - tend to have a healthier immune system that differs from others who don't develop those antibodies," Stamatatos explained, saying that these antibodies target only a few regions of HIV which is good from the standpoint of vaccine development. "It gives us less to target," he said.
In addition, the new findings show that these antibodies are generated much sooner than previously thought, in some cases as soon as a year after infection.
"These studies provide a strong rationale to begin teasing out the early immunological signals that allow some individuals, but not others, to mount broadly reactive neutralizing antibody responses," adds co-author Galit Alter, Ph.D.
"Now we know that these broadly-reactive neutralizing antibodies don't develop simply by chance and we can work to understand what makes this 30% of the HIV-infected population different," Stamatatos explained. By understanding that, we can hopefully use that information to design new immunogens and immunization protocols that can mimic the early events that lead to the development of such antibodies during natural infection."

Fulbright Award has UC educator examining health challenges in China

Tue, 04 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The New Year has a University of Cincinnati professor sharing his vast and vital research background on health education in a new location. Randall Cottrell, a UC professor of health promotion and education in the College of Education, Criminal Justice, and Human Services (CECH), is spending the winter and spring academic quarters at Zhejiang University in Hangzhou, China. He says he is one of only two public health educators nationally to receive a Fulbright Scholar Award to explore health education efforts in China and share research about health education programs in the United States.

Cottrell's Fulbright experience will involve teaching a foundations of health education course and a health education behavioral theory course to graduate-level Chinese public health and medical students. He spent months trying to learn Mandarin, but all of his classes will be taught in English, the official second language of China. He will also be accompanied by a Mandarin translator for presentations outside the university.

In addition to teaching, Cottrell's research project will explore cross-cultural comparisons in the health knowledge, attitudes and behaviors of Chinese and U.S. students. He may also be involved in research related to tobacco control and prevention.

Cottrell also visited Beijing, China last May as part of a delegation representing the American Association for Health Education (AAHE), of which he is a past president, and the Society for Public Health Education (SOPHE), of which he is a past board member. During that visit, he spoke with Chinese high school students.

When we talked with the Chinese students, they said that stress was their greatest health issue, and teachers agreed that there was tremendous pressure put on students to succeed in school, Cottrell says. Students reported that they'd start their school day around 7 a.m. and did not return home until 5 p.m. They were then expected to continue at least four or five hours of study daily at home after school. Some reported having no more than an hour of free time in the day, says Cottrell.

As for the adults, Cottrell says smoking is still the top health issue among Chinese adults, followed by high blood pressure. He says that China also is encouraging health education efforts to combat obesity and HIV. Cottrell will be sharing his expertise on health education programs aimed at preventing negative health behaviors. It also seems like a country that is ripe for health education, so that's a good fit for me. They can use my skills and hopefully, I can contribute and help to some extent, he says.

For me personally, this is an opportunity to learn more about the culture and the health education efforts of one of the most fascinating countries in the world, Cottrell says. It is truly an honor to travel to another country to share my knowledge, love and enthusiasm for the health education profession. He will also be spending his Fulbright experience in China with his wife, Karen, who is on leave as a health education teacher for the Lakota School District.

Cottrell has written textbooks on stress management, weight control, foundations of the profession and most recently, research methods.

Established in 1946, the Fulbright Program is the flagship international educational exchange program sponsored by the U.S. government. The program operates in more than 155 countries.

Cottrell joined the faculty at the University of Cincinnati in 1987. His two sons, Kory and Kyle, are both alumni of the UC College of Business.

Surprising AIDS-treatment benefits, prevention strategy in epidemic regions of Africa

Wed, 01 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Two teams of researchers at UC San Diego and other U.S. and African universities and the World Bank have documented significant spillover benefits of a drug therapy to combat AIDS symptoms and a novel prevention strategy that focuses on girls in Sub-Saharan Africa, an area with two-thirds of the world's HIV infections.

A recently published paper in Public Economics documents a dramatic Lazarus effect in AIDS-affected households in rural Kenya when infirmed members received anti-retroviral therapy (ART). The study found that not only did the health of those treated improve, but the households also began to accumulate livestock and other assets and they increased their investments in the education of their children.

Most successful AIDS relief initiatives have been lopsided in their focus on anti-retroviral therapy, but behavioral dimensions of the epidemic are equally significant, said Joshua Graff-Zivin, co-author of the study and associate professor of economics at UC San Diego's School of International Relations and Pacific Studies (IR/PS). Anti-retroviral therapy may be achieving much more far-reaching impacts than just the medical benefits, and anti-retroviral therapy may help the continent escape a much broader set of behavioral poverty traps that would otherwise arise from stratospheric HIV-prevalence rates.

The study was supported by a partnership of the U.S. Agency for International Development. Graff-Zivin worked with Harsha Thirumurthy, assistant professor of health economics at the University of North Carolina, and Markus Goldstein, a senior economist at the World Bank. The team showed that when affected members of rural Kenyan households received the drug therapy, a range of household investment indicators suddenly improved. In addition, children's nutritional status went up and their school attendance increased more than 20 percent within six months after treatment was initiated for the adult patient.

This Lazarus effect, whereby those who had expected a swift decline and death are granted a new lease on life by treatment, suggests that without effective anti-retroviral treatment, the epidemic may be having pervasive negative effects on people's willingness to think long-term and to invest for the future, Graff-Zivin said. This study shows that effective treatment yields significant economic dividends such as improved capital investment. Based on our latest field research we also think anti-retroviral therapy enhances environmental stewardship and a host of other positive effects as households switch from a sense of hopelessness to planning for their long-term futures.

In a separate study conducted in the southern African nation of Malawi and recently published in

30 years on in the epicenter of the African AIDS epidemic

Fri, 12 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) The impact of 30 years of HIV on an area once described as the epicentre of the African AIDS epidemic will be discussed at a lecture hosted by the University of East Anglia (UEA) in London this month.

Progressive declines in agricultural production, with dire consequences for rural livelihoods, were originally predicted as a result of the long-term effects of HIV and AIDS in central and south western Uganda. However, recent research has shown that those forecasts have not come true.

The lecture 30 years into the HIV epidemic in South West Uganda and the rural economy hasn't collapsed. What happened? takes place on November 25 at UEA London, ahead of World AIDS Day on December 1. Prof Janet Seeley, of the university's School of International Development, will report on research carried out over the last three decades that has looked in more depth at the impact of HIV-related infection and AIDS-related deaths on individuals, communities and livelihoods, in order to contribute to the design of policies and programmes that address the ongoing issues.

Prof Seeley, who has studied the effects of HIV/AIDS on rural communities in East Africa, in particular Uganda, for more than 20 years, will explore the reasons why rural livelihoods have proved to be much more resilient than had been expected in this region, and suggest lessons for forecasting.

In the mid 1980s south-western Uganda and north-western Tanzania were often referred to as the epicentre of the African AIDS epidemic. When first identified HIV/AIDS was of concern as a possible adverse factor in social and economic development because of its specific impact in the 15-50 age group.

The research carried out by Prof Seeley and colleagues Prof Tony Barnett, of the London School of Economics and Political Science, and Prof Stefan Dercon of the University of Oxford, has found that HIV/AIDS has sometimes thrown households into disarray and poverty, but more often it has reduced development and kept households poor.

People have undoubtedly suffered terrible personal loss and distress, but those who have survived have drawn on support from family and friends and from local organisations to rebuild livelihoods. People have shown resilience and managed, said Prof Seeley. For some the epidemic has been devastating but often on a household level families have adapted and the community as a whole has done better than expected. While there have been so many other crises, drought and crop failure for example, there have been new opportunities as well.

People have been changing occupations, diversifying, not necessarily because of HIV but because of diseases that have affected their crops and animals and pressures to earn a cash income. They haven't only had to face HIV/AIDS, they've had problems inflicted by drought, pests and other human disease.

However, Prof Seeley stresses that poverty remains, as does the endemic HIV disease, and that the health status of the population is poor and life remains hard.

The effects of HIV/AIDS are not as apparent with the simple clarity once assumed because so much else is going on in any society. For policymakers this research shows that they cannot focus on one aspect and assume everything can be attributed to that - too often HIV is reduced to a medical issue, but so much of what is going on is to do with social lives and behaviour, not just sexual behaviour. Resources often go to the medical and not the social support.

The challenge for development policy and implementation continues to be to find ways of addressing the persistent poverty and deprivation, which in part contributed to the particular manifestation of the AIDS epidemic in this region.

HHS agencies partner with PEPFAR to transform African medical education

Thu, 07 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The U.S. Department of Health and Human Services is partnering with the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) with a plan to invest $130 million over five years to transform African medical education and dramatically increase the number of health care workers.

Through the Medical Education Partnership Initiative (MEPI), grants are being awarded directly to African institutions in a dozen countries, working in partnership with U.S. medical schools and universities. The initiative will form a network including about 30 regional partners, country health and education ministries, and more than 20 U.S. collaborators.

The program is designed to support PEPFAR's goals to train and retain 140,000 new health care workers and improve the capacity of partner countries to deliver primary health care.

We must dramatically transform African medical education to increase the number of qualified care providers available and develop the scientific expertise needed for research and innovation, said Ambassador Eric Goosby, U.S. Global AIDS Coordinator at the Department of State. By engaging country health and education ministries, MEPI will strengthen national plans to improve medical instruction and bolster the overall health care delivery systems. As we transition PEPFAR-supported HIV efforts from an emergency response to a more sustainable effort, we need to develop the expertise necessary for evidence-based decision making on the local level. This expertise will empower countries to lead health programs and fulfill their responsibility for the health of their people.

Several components of the National Institutes of Health joined PEPFAR in funding the initiative, which will be administered by Fogarty International Center of the NIH and the HIV/AIDS Bureau of the Health Resources and Services Administration (HRSA).

Eleven programmatic awards, largely funded by PEPFAR, will expand and enhance medical education and research training in the field of HIV/AIDS. Eight smaller non-HIV/AIDS awards, funded by the NIH Director's Common Fund, with additional support from several NIH institutes, will encourage the development of expertise in topics such as maternal and child health, cardiovascular diseases, cancer, mental health, surgery and emergency medicine. Over a five-year period, MEPI intends to provide up to $10 million for each programmatic award, up to $2.5 million for each linked project and up to $1.25 million for each pilot grant.

Non-communicable diseases, such as maternal-child health issues, cardiovascular disease, cancer, and mental illness, represent the fastest growing causes of morbidity and mortality in sub-Saharan Africa, said NIH Director Francis S. Collins, M.D., Ph.D. We at NIH are delighted to join hands with our colleagues in PEPFAR to help build research and clinical capacity in these important areas of human health.

A coordinating center is being established to link the African sites and their U.S. partners, leverage shared resources and provide technical expertise. A Web-based platform will be developed to allow all partners to share data and outcomes. The platform will facilitate evaluation and provide a gateway to maximize the initiative's global impact. MEPI will enable participating institutions to strengthen their information technology infrastructure, support distance education and data sharing, and encourage the establishment of clinical registries to inform research and health care decision making on national levels. The coordinating center will also form an African leadership network to guide and advocate for the initiative.

HRSA's decades of experience working in HIV/AIDS through the Ryan White HIV/AIDS Program have highlighted the critical need for enhanced medical education and training to provide quality care to people affected by HIV/AIDS in rural and underserved communities. We are proud to collaborate with PEPFAR and NIH to advance medical education in Africa through this initiative, as well as continue supporting the on-going care and treatment and health system strengthening activities, said Mary K. Wakefield, Ph.D., R.N., HRSA administrator.

NIH funding is being provided by the Common Fund, Office of AIDS Research, Office of Research on Women's Health, National Heart, Lung and Blood Institute, National Human Genome Research Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Institute of Nursing Research.

Here is the complete list of MEPI awards and collaborating partners:

Programmatic Awards:

Botswana: University of Botswana, in partnership with Harvard School of Public Health and the University of Pennsylvania

Doctors at University of Colorado School of Medicine to train African doctors in AIDS care

Thu, 07 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The HIV epidemic continues to grow, especially in Africa where it has orphaned millions of children and decimated entire communities. In this environment, funding to train African health care providers is critical.

The U.S. Department of Health and Human Services is partnering with the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) to invest $130 million over five years to transform African medical education and dramatically increase the number of practicing health care workers. The University of Colorado School of Medicine will receive $1.9 million in federal grant funding to support this work. Faculty from the University of Colorado will travel to Zimbabwe to train medical students about HIV under funding from this NIH grant.

The Medical Education Partnership Initiative (MEPI) will award grants directly to African institutions in a dozen countries; the African institutions will work in partnership with U.S. medical schools and universities. The initiative will form a network of approximately 30 regional partners, country health and education ministries, and more than 20 U.S. collaborators. University of Colorado School of Medicine will collaborate with the University of Zimbabwe College of Health Sciences in one of the programmatic awards announced today. The Colorado-Zimbabwe collaboration, called the Novel Education Clinical Trainees and Researchers (NECTAR), will improve medical student HIV education in Zimbabwe. Dr. Thomas Campbell, MD, Professor of Medicine, is the Principal Investigator for the University of Colorado. Drs. Eva Aagaard, Director of the Academy of Medical Educators, Lucy Bradley-Springer, Director of the Mountain Plains AIDS Education and Training Center, Suzanne Brandenburg, Director of the Internal Medicine Residency Program, and Nancy Madinger, Director of the Infectious Diseases Fellowship Program at the University of Colorado School of Medicine will work with Dr. Campbell to administer and implement the program. Bonnie Walters, Executive Director of the Evaluation Center in the School of Education and Human Development, and her colleagues will monitor the impact of NECTAR on medical education in Zimbabwe.

The University of Colorado is widely recognized for the outstanding teachers and clinicians among our faculty, said Campbell. It is very exciting that we will now have this opportunity to share our teaching skills with our Zimbabwean colleagues to help them improve medical education in Zimbabwe. As NECTAR is implemented, interested UC faculty from diverse areas of medicine will have opportunities to participate in activities at the University of Zimbabwe including lecturing, bedside teaching and clinical and research mentorship.

We must dramatically transform African medical education to increase the number of qualified care providers available and develop the scientific expertise needed for research and innovation, said Ambassador Eric Goosby, U.S. Global AIDS Coordinator at the State Department. By engaging country health and education ministries, MEPI will strengthen national plans to improve medical instruction and bolster the overall health care delivery systems. As we transition PEPFAR-supported HIV efforts from an emergency response to a more sustainable effort, we need to develop the expertise necessary for evidence-based decision making on the local level. This expertise will empower countries to lead health programs and fulfill their responsibility for the health of their people.

Eleven programmatic awards, largely funded by PEPFAR, will expand and enhance medical education and research training in the field of HIV. Eight smaller, non-HIV awards, funded by the NIH Director's Common Fund, with additional support from several NIH institutes, will help develop expertise in topics such as maternal and child health, cardiovascular diseases, cancer, mental health, surgery and emergency medicine. Through NECTAR, UC Faculty will support PEPFAR goals to train and retain 140,000 new health care workers and improve the capacity of partner countries to deliver primary health care.

HRSA's decades of experience working in HIV/AIDS through the Ryan White HIV/AIDS Program have highlighted the critical need for enhanced medical education and training to provide quality care to people affected by HIV/AIDS in rural and underserved communities. We are proud to collaborate with PEPFAR and NIH to advance medical education in Africa through this initiative, as well as continue supporting the on-going care and treatment and health system strengthening activities, said Mary K. Wakefield, Ph.D., R.N., HRSA administrator.

Unprecedented effort to seek, test and treat inmates with HIV

Thu, 23 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Twelve scientific teams in more than a dozen states will receive National Institutes of Health (NIH) grants to study effective ways to prevent and treat HIV/AIDS among people in the criminal justice system. The grants, announced today, will be awarded primarily by the National Institute on Drug Abuse (NIDA), with additional support from the National Institute of Mental Health (NIMH) and the National Institute of Allergy and Infectious Diseases (NIAID), all components of NIH. The research will take place over a five-year period.

These important and wide reaching research grants will focus on identifying individuals with HIV within the criminal justice system and linking them to highly active antiretroviral therapy (HAART) during periods of incarceration and after community re-entry, said NIDA Director Dr. Nora D. Volkow. We hope this effort will lead to decreased HIV/AIDS-related illness and death among those in the criminal justice system, as well as decrease HIV transmission in the community at-large, making an important impact on public health.

The seek, test and treat funding opportunity follows NIH-sponsored research conducted over the last few years which has indicated that identifying and offering treatment to all medically eligible HIV-positive individuals cannot only stop progression to AIDS and AIDS-related death, but can also help to prevent HIV transmission. These new grants will apply this strategy to the criminal justice system, where there is a high prevalence of HIV/AIDS and often poor access to treatment.

The newly funded research will compare different modalities of the seek, test, and treat strategy to identify, test, engage and retain HIV-positive offenders in treatment. Some of the projects will create and compare systems to better integrate and coordinate HIV management efforts within jails, prisons, health departments, universities, and community organizations. The grants will also support randomized controlled trials among large groups of HIV-positive parolees and probationers comparing varied approaches for linking them to screening, treatment and social services in their communities.

We are learning that treatment can be one of the most powerful forms of prevention, said NIMH Director Dr. Thomas Insel. But treatment of HIV-infected men and women during or after incarceration is a challenge, especially when many have co-occurring mental or substance abuse disorders. We know that patients will stay connected to HIV care if their mental health improves. NIMH's project involves intensive case management for African-American and Latino parolees in Oakland, California.

The grants will support research in a diverse group of jails and prison systems, including the Los Angeles County Jail; the Cook County Jail in Chicago; the Rikers Island correctional facility in New York City; jail facilities in Washington, D.C., as well as prison systems in Illinois, North Carolina, Texas, Wisconsin and Rhode Island. One of the grants will compare levels of care and adherence to HAART treatment among HIV-positive injection-drug using detainees in Hanoi, Vietnam, a city with a high rate of HIV infection related to drug use. Two of the projects will study the effectiveness of medication used to treat heroin addiction among HIV-positive injection drug users who are transitioning to home communities.

The strategy of providing widespread, voluntary testing for HIV infection, identifying individuals infected with the virus and better linking those patients to antiretroviral treatment and medical care is one that NIH is pursuing in a number of different populations, said NIAID Director Dr. Anthony S. Fauci. It is a potentially viable way to reduce HIV transmission and improve the health of those infected with the virus.

Currently, an estimated 1.1 million people in the United States are infected with HIV. Since the late 1990s, the number of new HIV infections has remained relatively stable with approximately 56,000 new infections reported annually. The funding opportunity, Seek, Test, and Treat: Addressing HIV in the Criminal Justice System, represents NIH's largest research initiative to date to aggressively identify and treat HIV-positive inmates, parolees and probationers and to help them continue care when they return to their communities. Close to $50 million dollars in grants over a five-year period are expected under this research initiative.

About four of every 10 AIDS deaths are related to drug abuse. Each year, an estimated one in seven individuals infected with HIV passes through a correctional facility suggesting that a disproportionate number of people in the criminal justice system are infected with the virus.

Vitamin A increases the presence of the HIV virus in breast milk

Thu, 26 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Vitamin A and beta-carotene supplements are unsafe for HIV-positive women who breastfeed because they may boost the excretion of HIV in breast milk---thereby increasing the chances of transmitting the infection to the child, a pair of new studies suggest.

Epidemiologist Eduardo Villamor of the University of Michigan School of Public Health says transmission of HIV through breastfeeding happens because breast milk carries viral particles that the baby ingests. Supplementing HIV-positive women with vitamin A and beta-carotene appears to increase the amount of the virus in milk.

This may be partly because the same nutrients raise the risk of developing subclinical mastitis, an inflammatory condition which causes blood plasma to leak into the mammary gland and viral particles to then leak into the milk, he says.

Villamor's findings appear in two separate articles in the American Journal of Clinical Nutrition and the Journal of Nutrition. The results are significant because they provide biological explanations for a previous report that supplementation with these nutrients increased chances of mother-to-child HIV transmission.

So there are now strong arguments to consider the implications of supplementation to pregnant or lactating women who are HIV-positive, said Villamor, associate professor of epidemiology and environmental health sciences. It does not look like it's a safe intervention for them.

Mother-to-child HIV transmission is a huge problem in developing countries where HIV is prevalent, Villamor said. In 2008 alone, there were 430,000 new infections and more than 95 percent of those resulted from mother-to-child transmission. Most were in sub-Saharan Africa.

In one of the studies, 1,078 HIV-infected women were divided into four groups. The test groups received either 5,000 IU of vitamin A and 30 mg of beta-carotene everyday during gestation and the lactation period, or a control regimen. The dose for beta-carotene was higher than the amount usually provided by the diet, according to Villamor. Smaller doses might not have the same effect.

Villamor said tests trying to separate the effects of each nutrient showed that beta-carotene seemed to increase the amount of HIV in breast milk independent of vitamin A, but an effect of vitamin A alone cannot be ruled out. The findings are potentially controversial because vitamin A is an important supplement for postpartum women in countries where HIV infection is highly prevalent, but supplementation programs may not take into account a woman's HIV status.

The takeaway is that daily supplementation of HIV-infected pregnant or lactating women with vitamin A and beta-carotene at the doses tested is probably not safe and efforts need to be strengthened on preventing mother-to-child transmission through other interventions such as anti-retroviral regimens, Villamor said.

UofL receives $3.15 million grant from Helmsley Charitable Trust

Thu, 05 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The University of Louisville has received a $3.15 million grant from the Leona M. and Harry B. Helmsley Charitable Trust to support the UofL James Graham Brown Cancer Center and cancer research taking place in Owensboro. The grant will be matched with state Bucks for Brains funding to bring more than $4.5 million to the Owensboro Cancer Research Program (OCRP).

When we established this program in partnership with Owensboro Medical Health System (OMHS) in 2006, we envisioned other significant organizations joining us in our effort to create and develop novel approaches to preventing and treating cancer, said Dr. James Ramsey, president of the University of Louisville. This gift from the Helmsley Trust moves our vision forward and is recognition for the importance of the work taking place here.

We are excited to see the fine work of the James Graham Brown Cancer Center and Owensboro Medical Health System expand through this public/private initiative, noted John Codey, trustee of the Helmsley Charitable Trust. The promise of plant-based pharmaceuticals and vaccines to dramatically improve healthcare at reduced cost is both exciting and critically important.

The grant and state matching funds will be used to create an endowed faculty position for a nationally recognized researcher in plant-based pharmaceuticals, as well as creating two new faculty members to expand and enhance the research program.

The tobacco-based process involves inserting genes needed for drug development into the tobacco genome. The leaves are then harvested, processed and purified to derive a key ingredient.

Projects underway at OCRP include, but are not limited to, the development of a plant-based vaccine to prevent HIV, understanding how changes in the calcium-signaling pathway of stem cells impacts the development and continued growth of lung cancer cells, as well as determining whether the interaction of the heavy metal cadmium with tobacco-derived carcinogens contributes to the development of lung cancer in smokers.

Plant-based pharmaceutical systems have a number of advantages, said Dr. Donald Miller, director of the James Graham Brown Cancer Center. The costs for starting materials are low, which translates into a lower production cost. The materials are readily available, meaning that we are able to increase production levels relatively quickly. Additionally, plant-based therapies have fewer issues with potential contamination than those utilizing other materials such as animal or human pathogens.

The collaboration between UofL and OMHS is greatly enhanced because of Kentucky BioProcessing (KBP), located in Owensboro. KBP is a world leader in the development and execution of scalable processes for commercial scale production of plant-made pharmaceuticals. Established by OMHS in 2006, KBP has developed a network of relationships with leading PMP researchers from across the globe.

We have a tremendous amount of resources in the Owensboro region to assist in the research to develop new therapies to prevent or treat cancer, said Jeff Barber, Dr. PH, president and chief executive officer of OMHS. It is exciting that we have the opportunity to develop cancer cures that could someday benefit patients around the globe.

The Owensboro Cancer Research Program is devoted to unlocking the potential of plant-made pharmaceuticals. The research and drug development program takes advantage of the natural products and agricultural industries in the Owensboro region to address diseases impacting the area, especially those that are tobacco-related. Ultimately, the partnership's goal is to create less expensive drugs for cancer prevention and treatment.

Right now researchers with the James Graham Brown Cancer Center and OCRP are working to develop a second-generation cervical cancer vaccine grown in tobacco plants in order to make it affordable to millions of women worldwide. A vaccine of this type will be most beneficial in women in rural parts of the United States, India and Sub-Saharan Africa.

NIH-funded study finds early HAART during TB treatment boosts survival rate in co-infected people

Thu, 22 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A clinical trial in Cambodia has found it possible to prolong the survival of untreated HIV-infected adults with very weak immune systems and newly diagnosed tuberculosis (TB) by starting anti-HIV therapy two weeks after beginning TB treatment, rather than waiting eight weeks, as has been standard. This finding by scientists co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the French National Agency for Research on AIDS and Viral Hepatitis, brings physicians closer to optimizing the treatment of severely immunosuppressed individuals with HIV-TB co-infection. The findings were presented today at the XVIII International AIDS Conference in Vienna by principal investigators Francois-Xavier Blanc, M.D., Anne E. Goldfeld, M.D., and Sok Thim, M.D.

These results are just one example of how our best science can advance the treatment of an important disease, TB, that exacts a huge toll among HIV-infected individuals, says NIAID Director Anthony S. Fauci, M.D. With an estimated 1.4 million HIV-infected individuals developing TB in 2008 alone, we must continue to pursue 21st-century solutions to the scourge of HIV-TB co-infection, as well as other diseases that afflict HIV-infected people.

Individuals with HIV-TB co-infection in resource-limited countries frequently come to the attention of healthcare professionals for the first time when HIV already has severely damaged their immune systems. Such people often die during the first few months after beginning TB treatment. Clinicians agree that starting anti-HIV therapy during that short window can stave off death for some patients, but data on the best time to start have proven inconclusive and opinions have varied. The dilemma is that starting anti-HIV therapy before the TB infection is under control can cause the patient to become very sick and even die from a condition known as Immune Reconstitution Inflammatory Syndrome, but starting anti-HIV therapy too late may allow the patient to die from HIV infection. TB accounted for nearly a quarter of HIV-related deaths worldwide in 2008.

The clinical trial, called the Cambodian Early versus Late Introduction of Antiretroviral Drugs (CAMELIA), or ANRS 1295, launched in January 2006 at five sites in Cambodia, a country with a high prevalence of TB and HIV. The study staff enrolled 661 volunteers ages 18 and older with newly diagnosed HIV-TB co-infection and very weak immune systems (measured as fewer than 200 CD4+ T cells per cubic millimeter of blood). The participants all began receiving treatment for TB and were assigned at random to begin antiretroviral therapy for HIV either two weeks later or eight weeks later. The volunteers received powerful antiretroviral drug cocktails known as highly active antiretroviral therapy, or HAART. Study staff followed the participants for 50 weeks after the last volunteer had enrolled in the trial, performing clinical exams and biological tests at frequent intervals to monitor participants' health and safety.

By the end of the follow-up period, 59 out of 332 participants who had started HAART two weeks after beginning TB treatment had died, while 90 out of 329 participants who started HAART eight weeks after beginning TB treatment had died. This 33 percent difference was statistically significant, leading the principal investigators to conclude that starting HAART two weeks after beginning TB treatment, rather than waiting eight weeks, boosts the chance of survival for people with HIV-TB co-infection and severely damaged immune systems.

New global report launched by the International AIDS Society recommends a new paradigm for treating injecting drug users: 'Seek, test, treat and retain'

Thu, 22 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Thursday, 22 July, 2010 (Vienna, Austria)-- Against the backdrop of some of the globe's fastest growing HIV epidemics in Eastern Europe and Central Asia, a report launched today at the XVIII International AIDS conference (AIDS 2010) in Vienna makes the case for a new model for scaling up treatment and prevention of HIV amongst Injecting Drug Users (IDUs).

The report, Prevention and Treatment of HIV/AIDS amongst Drug Using Populations: A Global Perspective, advocates a science based approach and stresses the urgent need to increase access and expand take up of highly active anti retroviral therapy (HAART) among drug using populations to improve health and reduce new infections. (1)

Increasing evidence supports the idea of expanding the implementation of outreach to high-risk, hard-to-reach drug using populations (seek), to encourage HIV testing (test), to link HIV+ individuals to care (treat), and to sustain these individuals in care (retain). The seek, test, treat, and retain model is also deliverable within the criminal justice system.

The evidence is in, individuals with and without a history of injection drug use derive similar survival benefit from HAART. There is an urgent need to treat drug users, not abuse them as much of the current drug policies do, said Dr Julio Montaner, President of the International AIDS Society. Sound public health policy demands that we increase access to HIV treatment and prevention for this population.

Two decades of experience have demonstrated that needle exchange programs are a proven way of preventing HIV infection amongst injecting drug users (IDUs). The report outlines how programs can increase this effectiveness by scaling up a comprehensive package of harm reduction interventions.

Offering Opioid Substitution Therapy (OST), such as methadone or buprenorphine, significantly decreases HIV acquisition and transmission and increases the chances of HIV positive people who inject drugs taking up and staying on highly active anti retroviral therapy (HAART), said Professor Dr Charles O'Brien, a researcher from the University of Pennsylvania and one of the contributors to the report. This in turn can lead to reductions in the community viral load and decrease new infections.

Wider uptake of HAART is associated with reduced community viral load and reduced transmission as well as individual survival. Not only does treatment offer health benefits for the individual, said Dr Montaner, but in diverse populations, we can now see that HAART is HIV prevention.

The selection of Vienna as the host city of the XVIII International AIDS Conference reflects the role the city has played in bridging Eastern and Western Europe. During the past week there has been a strong focus on Eastern Europe and Central Asia region, now home to what is the fastest growing HIV/AIDS epidemic in the world. Injecting drug use is the main driver of HIV infection in the region.

Some 65 per cent of HIV infections in Russia for instance, are through injecting drug use. The number of HIV infected people in Russia has increased tenfold in the past decade from an estimated 100,000 to one million. Eighty per cent of HIV positive people are under 30 years of age. Methadone is illegal in Russia.

The Russian government does not implement an evidence based approach to decision-making on public health, said Dasha Ocheret, spokesperson for the Eurasian Harm Reduction Network (EHRN). The prohibition of substitution treatment such as methadone is based on Soviet ideology and denies drug users the right to life saving treatment and prevention that exist in the vast majority of countries in the region. Methadone treatment began in Lithuania as far back as 1984.

Russian Government funds are used for policing rather than sound public health policy. All attempts by the Russian government over the past decade to control drug trafficking have been counterproductive and resulted in increased incarceration rates of people who use drugs and social exclusion and led to numerous deaths from overdoses and HIV and TB infections.

The report argues that it is now recognized that a punitive approach leads to the creation of incubators for HIV, HCV and TB in prisons.

We've been witness this week in Vienna to what is an all too familiar story: the unacceptable criminalisation and stigmatisation of a group of people, in this case, people who inject drugs, said Montaner. As a result of repressive drug policies and frankly, appalling public health policy in many parts of Eastern Europe, people who inject drugs are now shouldering the burden of an HIV epidemic that shows all the signs of moving into the wider community.

On the other hand we've also heard success stories in the region that give hope to scientists, researchers and policy makers who are committed to addressing HIV and injecting drug use based on sound scientific empiric evidence along the lines suggested in the report we have released today, concluded Montaner.

The report's recommendations include:

Mother-to-child HIV transmission rate falling, but more can be done

Thu, 22 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Transmission of HIV to children before or at birth has dropped dramatically around the country in the last decade since the advent of powerful new therapies. That certainly is true for Florida, where each year, fewer than 10 babies are born with the disease despite the fact that more than 600 HIV-positive women each year, on average, give birth.

Still, more can be done to even further reduce the number of babies born with the disease, say pediatric HIV experts at the University of Florida who this week presented their work during the 18th International AIDS conference in Vienna, Austria.

This is one of those diseases for which we learned how to prevent transmission. We need to make full use of this method and our energies need to be focused on the effort, said lead researcher Dr. Mobeen Rathore, a professor and chief of pediatric infectious diseases and immunology at the University of Florida College of Medicine-Jacksonville, and director of the UF Center for HIV/AIDS Research, Education and Service.

Around the United States, the decreasing number of pediatric infections is a direct result of the advent of powerful anti-HIV therapies in the mid-1990s and the establishment of protocols by the Centers for Disease Control and Prevention to treat pregnant women who are infected, and their babies.

Increased HIV-testing outreach and education efforts have also paid off. And CDC guidelines for opt-out HIV-testing for pregnant women mean testing is a routine part of their care, and women would have to specifically decline it. Rapid testing during labor and delivery gives one last chance to administer therapies that can prevent transmission.

In Florida, the Targeted Outreach for Pregnant Women Act of 1998 was enacted to help improve prenatal care and reduce the number of babies with HIV or prenatal drug exposure.

After New York, Florida has the second highest number of babies born to HIV-positive women. The state began monitoring the number of HIV-exposed babies in 2006. Up to 2008, a total of 2,374 cases of pediatric HIV/AIDS have been reported in Florida. So far this year, just one case has been reported.

The reduction of mother-to-child HIV transmission is one of the biggest success stories of the HIV epidemic, said Thomas Liberti, chief of the bureau of HIV/AIDS in the Florida Department of Health. The question is, 'How low can we go?'

The UF researchers teamed with colleagues in the Florida Department of Health Perinatal Prevention Division to review pediatric HIV data for the period from 2002-09, and found 102 cases.

Despite the many effective measures in place to help prevent HIV-transmission to babies, there are missed opportunities, the researchers found.

Mothers of half of the infected babies tested positive for HIV before becoming pregnant. But some refused or neglected to take the medications that could have kept their babies HIV-free. Some had no prenatal care, and so did not receive available treatments.

Some women were HIV-negative at the start of their pregnancy, but became infected afterward. Others were diagnosed with HIV only after the birth of their babies. Repeat testing during pregnancy and rapid testing during labor and delivery would have alerted health care providers.

The study shows that for some women, the issue might not be a lack of availability of medical services. Mental illness, intravenous drug use and incarceration and other risk factors associated with increased risk of HIV infection affected about one-third of the women who delivered infected babies. Mental health and substance abuse issues often prevent women from taking advantage of medical care or adhering to a treatment regimen prescribed by their physicians.

Finding creative ways to address issues such as the shortage of mental health-care providers will help women and their babies get needed care, the researchers said.

The health department has already begun discussions with the Centers for Disease Control and Prevention to discuss steps that can be taken to further reduce mother to child HIV transmission.

Many of our patients have mental health and other life issues, so if we do not address them, the treatment protocol will not be effective, Rathore said. This is an intervention that has the opportunity to work better.

$9M NIH grant renewal awarded to Case Western Reserve/UHCMC Center for AIDS Research

Wed, 21 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The Case Western Reserve University/University Hospitals Case Medical Center Center for AIDS Research (CFAR) announced today it has received a five-year renewal grant from the National Institutes of Health (NIH) for $9 million. The CFAR provides clinical and technological support to researchers working on HIV-related projects at Case Western Reserve, University Hospital Case Medical Center, MetroHealth Medical Center, Cleveland Clinic, and several international sites.

For the last sixteen years the Case Western Reserve University/University Hospitals Case Medical Center CFAR has been a leader in the advancement of AIDS-related research worldwide, says Jonathan Karn, PhD, the Reinberger Professor of Molecular Biology, Chair of the Department of Molecular Biology and Microbiology, and Director of the Case Western Reserve University/University Hospitals Case Medical Center CFAR. With the five-year extension of this grant, we look forward to expanding our research into questions of how HIV causes disease, how to develop new strategies to eradicate the virus from infected individuals, and how to limit transmission of the virus. We will also continue to develop our outstanding programs on HIV in Africa, building on our 20 year collaboration with Makerere University in Uganda, and our unique national and international clinical research capabilities.

The funding will also support new initiatives on links between HIV and cancer. The CFAR takes a leading role in faculty development by providing research awards to junior faculty and core support for HIV/AIDS research programs at Case Western Reserve. One of the most distinguished centers at the University, and rated in the top 20 AIDS programs nationwide, the CFAR renewal is a reflection of the advancements made in the translational research of an ever-expanding spectrum of AIDS-related activities which now engage the efforts of more than 160 faculty with a combined annual research budget of $20 million.

This welcome award recognizes the excellence in HIV/AIDS research and care that reflect the longstanding commitment of our institutions, our faculty and our staff to the challenges posed by this pandemic. The AIDS research and care program here in Cleveland is now entering its 29th year and for 23 years now has also sustained a major engagement in HIV research and care in the developing world that is so hard hit by the medical, social and fiscal tragedies of AIDS. The new directions of our CFAR are targeting the critical problems that now face persons with HIV infection worldwide and with this continued funding, the CFAR's research and care program is well positioned to advance the field of HIV/AIDS research with the shared goal of eradicating infection and ending its pandemic spread, says Michael Lederman, M.D., Scott R. Irkley Professor of Medicine at Case Western Reserve, infectious disease specialist at University Hospitals Case Medical Center and Associate Director of the CFAR.

There are currently 17 CFARs located at leading academic and research institutions throughout the U.S. which bring together the leading HIV investigators in the country. Within this elite group, the Case Western Reserve University/University Hospitals Case Medical Center CFAR is widely recognized for its leadership in HIV pathogenesis and international studies. Established in 1994, it has proactively engaged in clinical and international research in addition to the training of young researchers both on a national and international level. The CFAR works in conjunction with six other Case Western Reserve centers and departments including the Center for Global Heath and Disease, Tuberculosis Research Unit, Case Comprehensive Cancer Center, Center for Medical Mycology, Law-Medicine Center and Department of Bioethics.

Among the nation's leading academic medical centers, University Hospitals Case Medical Center is the primary affiliate of Case Western Reserve University School of Medicine, a nationally recognized leader in medical research and education.

HIV/AIDS treatment curbs spread of disease: UBC-BC CfE study

Mon, 19 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The BC Centre of Excellence in HIV/AIDS (BC-CfE) published an important study today in the globally respected Lancet medical journal. The study strongly reinforces the view that the benefits of highly active antiretroviral therapy (HAART) extend beyond treatment of the virus to significantly preventing the transmission and spread of HIV.

Recognized as the gold standard treatment for HIV, HAART uses a combination of drugs to stop HIV from progressing to AIDS, extends life expectancy, and significantly reduces HIV-related deaths in diagnosed individuals.

The expansion of HAART treatment plays an important role in the health of British Columbians with HIV, preventing HIV transmission and maximizing public health resources, said Gordon Campbell, Premier of British Columbia. Based on HAART's effectiveness and ongoing research at the BC-CfE, Canada's leading HIV/AIDS organization, the government of B.C. is investing in improving access to HAART through innovative programs such as the Seek and Treat initiative.

The new study, funded by the U.S. National Institute on Drug Abuse (NIDA), found that increased levels of HAART treatment were associated with a decrease in community viral load and in new HIV diagnoses across British Columbia, particularly in populations with a history of injection drug use.

These study results reinforce the effectiveness of HAART in preventing transmission of HIV, and support extending the treatment as prevention model developed at the BC-CfE and now being rolled out in major centres in Canada, the U.S. and elsewhere, said Dr. Julio Montaner, study lead author and BC-CfE director. Montaner is also a professor and chair in AIDS research at the University of British Columbia and President of the International AIDS Society (IAS).

This BC-CfE study suggests expanded HAART coverage may curb the spread of HIV, said NIDA Director Dr. Nora D. Volkow. These findings are especially important when it comes to populations with a history of injection drug use, as we now have a tool to help reduce the spread of HIV among them.

Results of mathematical models have varied dramatically in their estimation of the potential impact of increased HAART coverage on HIV transmission, predicting anywhere from elimination to potential worsening of the HIV epidemic. Therefore, the present study was conducted to analyze, at the population level, the potential association between the expansion of HAART, viral load and new HIV diagnoses per year in a Canadian province with free access to HIV care. The population was then stratified for injection drug use status.

Data resulting from BC-CfE research showed that the number of individuals actively receiving HAART had a strong impact on overall viral load and new diagnoses in the community. As HAART coverage increased, new HIV diagnoses decreased; as HAART coverage stabilized, so too did viral load and new HIV diagnoses.

Retrovirus replication process different than thought

Thu, 15 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) How a retrovirus, like HIV, reproduces and assembles new viruses is different than previously thought, according to Penn State College of Medicine researchers. Understanding the steps a virus takes for assembly could allow development of a way to prevent the spread of retroviral diseases.

The team studied a chicken virus called Rous sarcoma virus that causes cancer in chickens and is similar to HIV.

The question is, how do retroviruses build new virus particles? asked Leslie Parent, M.D., Ph.D., professor of infectious diseases, department of medicine. There are no inhibitors of HIV assembly in clinical use. If we can determine how retroviruses are built, we can help stop the spread of infection through the creation of new drugs.

The start of the replication process is the production by the retrovirus of a protein called Gag. Prior to this study, it was thought the building process happened outside the nucleus in the cyctoplasm -- the material that fills the cell -- and then Gag protein was sent to the plasma membrane -- the outer boundary of the cell. The researchers discovered, however, that Rous sarcoma virus takes a detour through the cell nucleus before going to the cell membrane.

The Gag protein has a signal, which tells a receptor to take it into the nucleus. Once in the nucleus, Gag binds to the viral RNA. The viral RNA alters the structure of the protein, changing the way it folds. This new configuration triggers a different signal that allows the Gag to move out of the nucleus.

There's a sequence of events that has to happen in a very specific order, Parent explained. The Gag protein has to find its own RNA, build a virus particle around it, and then release it from the cell. Finding the viral RNA is the first committed step in the assembly process. By focusing on regulatory processes in assembly, researchers are looking for key events that, if disrupted, could stop the virus from spreading.

We want to understand the smallest building blocks of the virus particle, Parent said. If we interfere with the first step, the virus will never be released from the cell. Cells are complex, so we use the key elements in a test tube to figure out how Gag and the RNA interact.

This study built on a 2002 paper, which proposed a model for the Gag protein's entry into the nucleus. The researchers reported in the

Faith-based groups can aid response to HIV in Central America, study finds

Tue, 01 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Faith-based organizations such as churches and religious relief and development groups can play an important role in the response to HIV and AIDS in Central America, according to a new RAND Corporation report.

While the role of religious groups often is seen as limited because many do not support certain prevention measures such as condoms, researchers say building on the traditional role of faith-based groups provides an important opportunity to improve a range of services and support.

Faith-based organizations are important to HIV efforts in Latin America because they have a broad reach and influence, and have played critical roles providing support and care to those affected by the disease, said Kathryn Pitkin Derose, the study's lead author and a senior policy researcher at RAND, a nonprofit research organization. Not every community in Central America has health providers, but most have some type of faith-based organization.

Researchers say that faith-based organizations, which historically have played a key role in delivering health and social services in developing countries, could play an expanded role in helping raise awareness of HIV and reduce the stigma that surrounds HIV and AIDS.

In addition, faith-based organizations could advocate for greater access to health care and provide resources such as nutritious food and income-generating assistance to those with HIV, according to the study.

Although faith-based organizations' role in prevention remains controversial, RAND researchers concluded that most faith-based organizations could promote HIV testing in ways consistent with their overall mission.

If faith-based groups partner with health providers to provide testing, it would send a constructive message that HIV is a disease that is treatable and people should know their HIV status, Derose said.

HIV/AIDS in Latin America has been called the overlooked epidemic because it has been overshadowed by epidemics of larger scale and severity in sub-Saharan Africa and Asia. Although AIDS accounts for a small fraction of deaths in most Latin American countries, the economic effects can be magnified because AIDS often strikes adults during their most-productive years.

Advocates have called for improved efforts to combat HIV in Latin America to prevent the type of devastating outbreaks that have occurred in sub-Saharan Africa. However, most Latin American governments have not responded as vigorously as advocates believe is necessary.

RAND researchers examined the current and potential future role of faith-based organizations in HIV prevention and care in three Central American countries that, at the time the study began, had the region's highest prevalence of HIV -- Belize (2.5 percent), Honduras (1.5 percent) and Guatemala (0.9 percent). They visited the countries and interviewed officials from governmental health agencies, faith-based groups, other non-governmental organizations serving people with HIV, and bilateral assistance agencies. They also visited clinics, hospices and other HIV-related programs sponsored by faith-based organizations.

In the three countries studied, HIV affects mostly young adults, men who have sex with men and sex workers. In all three countries, but especially Guatemala, care for HIV and AIDS is not widely available, and hospitals and health care personnel with experience in the illness are located mainly in major cities.

Researchers found that governments tend to emphasize treatment more than prevention, although the need to sustain antiretroviral medication long term for those with HIV infection has not been addressed.

While researchers are optimistic about the potential for help from faith-based organizations, they recognize that substantial obstacles exist. Judgmental attitudes and limited engagement with gays, men who have sex with men and commercial sex workers may limit the effectiveness of faith-based organizations' HIV efforts. There also is no single structure that brings together all faith-based groups and this often makes coordination between faith and health sectors difficult, according to researchers.

There is a need for greater recognition among leaders of health and faith-based organizations of the unique and complementary strength that each sector can provide to the response to HIV and AIDS, Derose said. Public health leaders need to think creatively about ways to make effective use of the strengths and capabilities of faith-based organizations in addressing the challenges posted by the HIV epidemic.

Rare hybrid cell key to regulating the immune system

Mon, 24 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Toni BakerPublic Relations ManagerMedical College of Georgia706-721-4421 Office 706-732-0401 Beeper706-825-6473 Cell tbaker@mcg.edu

May 24, 2010

Rare hybrid cell key to regulating the immune system

AUGUSTA, Ga. - A cell small in number but powerful in its ability to switch the immune system on or off is a unique hybrid of two well-known immune cell types, Medical College of Georgia researchers report.

This is actually the first cell we know of that has this type of appearance in nature, Dr. Andrew Mellor, molecular geneticist and immunologist who co-directs MCG's Immunotherapy Discovery Institute, said of the cell that looks like a dendritic cell and a B cell but isn't really either.

The discovery of this rare hybrid could have implications for the efficacy of new therapies that manipulate these two cell types to treat diseases such as cancer and rheumatoid arthritis.

When MCG scientists first reported the human equivalent of this cell in Science in 2002, they called it a subset of the dendritic cell that clusters in high exposure areas such as the gut but also roams the body, looking for invaders like a virus or cancer. Dendritic cells show their find to T cells, telling them to ignore or attack by bringing trash-eating macrophages, natural killer cells and the like into the fight.

What seemed most unique about the subset is its ability to express indoleamine 2,3 dioxygenase, or IDO, to turn off T cells. IDO is an enzyme used by fetuses and tumors alike to escape the immune response.

The new studies show that is only part of the cells' distinctiveness. The cells also have the identifying markings of B cells, known for their ability to make antibodies against invaders. In fact, they found the IDO-presenting cells came from the same precursor cell as B cells. But, when the scientists looked at mice missing B cells, they still found the IDO-producing cells. Hence, the cell didn't need to produce antibodies to turn off T cells.

In reality, IDO-expressing cells have properties of both cells, said Burles A. Johnson III, an MCG M.D.-Ph.D. student and first author of the paper published online this week in PNAS. It looks like a B cell and it's not. It looks like a dendritic cell and it is and it isn't, Johnson said.

While their studies are in mice, the cells also are in humans, showing up in some unfortunate places such as the drainage system for tumors, melanoma or even HIV where they likely help the diseases survive.

They also may be showing up in new dendritic cell therapies designed to strengthen the immune response to cancer. If the therapies happen to include some IDO-expressing cells, those could end up helping the cancer, said Mellor, the paper's corresponding author. All you need is a few of these cells in your dendritic cell vaccine and you don't get stimulation any more, you get suppression, Mellor said.

Their confusing face could also cause hybrids to be lost in B cell-depleting therapies designed to lessen the immune system's attack on joints in rheumatoid arthritis. These therapies may also deplete IDO-expressing cells and decrease therapy effectiveness because you are eliminating cells that are there to help you, Johnson said.

This gives us new insight into why these therapies might not be working as well as we think they might, Mellor added. Long-term goals include figuring out how to manipulate the hybrid's activity to benefit patients.

The research was funded by the National Institutes of Health and the Germany-based pharmaceutical company Boehringer-Ingelheim. Mellor is a Georgia Research Alliance Eminent Scholar in Molecular Immunogenetics.

Dynamic detection technique for HIV

Wed, 19 May 2010 14:35:40 PST

( from http://www.rxpgnews.com ) A relatively simple electronic gadget could speed up HIV/AIDS diagnostics and improve accuracy particularly in parts of the world with very limited access to healthcare workers. The device is described in the International Journal of Biomedical Engineering and Technology.

Ali El Kateeb of the Electrical and Computer Engineering Department, at the University of Michigan, in Dearborn, explains that rapid blood tests for diagnosing HIV have become widely available but are prone to human error in reading the results. The currently available kits require a drop of blood placed in a well containing reactant test chemicals. A positive test produces a colored band perpendicular to a "control" bar that appears only if the test procedure was carried out correctly. El Kateeb points out that even such an apparently simple test must be carried out by a trained technician and in a clinic or laboratory.

Unfortunately, errors in reading the test pattern can occur and are particularly common in parts of the world where there is a dearth of qualified technicians. The result is that false positives that have a negative psychological effect on patients are common while false negatives mean patients thinking they are free of the virus will continue to infect others unwittingly.

Previously, El Kateeb had developed a static imaging device -, akin to a simple digital camera, that could be used to identify valid and positive test results using a built-in computer chip modified to run a dedicated pattern recognition program. The static approach was not entirely successful because it relies on precise manufacture of the test kit as well as accurate placement of the "eye" of the imaging device above the test kit. Now, El Kateeb has developed a "dynamic" version of the device that overcomes this significant drawback.

In the dynamic approach, the built-in software embedded on a Reconfigurable System-On-Chip, first determines the relative position of the detector's 384 × 288 pixel eye relative to the test kit well, illuminated by four LEDs, using a rapid analysis of pixel density in the captured image. The software then identifies the control bar and detects whether or not the perpendicular test bar is present regardless of their exact positioning within the well.

El Kateeb says this dynamic detection technique is 100% accurate in laboratory testing. The device is inexpensive, portable and self-contained and so could be made available to small clinics and pharmacies at low cost. Moreover, it requires no technician intervention, which will make it useful for rural areas in the developing world.

HHS Secretary Sebelius announces $1 billion in NIH Recovery Act awards for research construction

Fri, 14 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) U.S. Health and Human Services Secretary Kathleen Sebelius today announced one billion dollars of American Recovery and Reinvestment Act funds have been awarded to construct, repair and renovate scientific research laboratories and related facilities across the country. The National Institutes of Health (NIH) National Center for Research Resources (NCRR) administered the grants, which are expected to create or sustain jobs nationwide and to help foster scientific advances that may lead to improved human health.

A total of 146 grants to institutions in 44 states, the District of Columbia and Puerto Rico were awarded to upgrade and construct buildings, laboratory spaces and core facilities that are crucial to biomedical and behavioral investigators.

This unprecedented Recovery Act investment in research facility construction will not only give our world-class scientists the modern facilities they need for impact research, it will also help create and maintain jobs in varied business sectors and in all regions of our country, said Secretary Sebelius.

These awards are part of an overall $100 billion federal government investment in science, innovation and technology the Administration is making through the Recovery Act to spur domestic job creation in emerging industries and create a long-term foundation for economic growth.

These Recovery Act dollars will provide state-of-the-art facilities for hundreds of researchers to conduct cutting-edge science with the latest technologies, said NIH Director Francis S. Collins, M.D., Ph.D. At the same time, they will create job opportunities nationwide.

Highlighted below are four examples that provide a snapshot of how institutions coast-to-coast will use these funds to help advance studies in disease areas such as cancer, HIV/AIDS, autism, pediatric illnesses and other health disorders.

Renovation of Children's Health Research and Evaluation Facility, Indianapolis Nearly $8.5 million in grant funding will help to create a state-of-the-art facility for pediatric clinical research and to create a core facility of pediatric phenotyping laboratories and patient research resources at the Indiana University School of Medicine. Phenotyping is the use of epidemiologic, biological, molecular or computational methods to systematically select features of a disorder that might result from distinct genetic influences. The project will bring together a range of existing pediatrics laboratory programs into a single core to create collaborative, quantitative phenotyping of diseases and treatments.

The Genome Data Center Initiative, St. Louis The Washington University School of Medicine (WUSM) will use a $14.3 million award to build a world-class data center to support human genome research. WUSM has been involved in genome science since the inception of the field. Its genome center recently embarked on several ambitious projects to decode the genomics of hundreds of cancer patients and their tumors. The research has the potential to transform the diagnosis and treatment of cancer. The new 15,000 square-foot data center will support the computational power and storage needs that projects like these require.

The San Francisco Office of AIDS Renovation (SOAR) Project A grant of more than $9.5 million will allow three prominent United States-based HIV/AIDS prevention research units within the San Francisco Department of Public Health to increase their capacity to recruit, enroll and retain large, diverse populations of study participants efficiently and effectively, and to provide critical data on new HIV/AIDS cases to investigators worldwide. The SOAR project will provide researchers with the space and data needs required for large patient studies, improved security for records storage and space needed for training. The project also will have an impact on current and future biomedical HIV/AIDS research and training initiatives.

Cell and DNA Repository Renovation, New Brunswick, N.J. Data sharing is essential for expedited translation of research results into knowledge, products and procedures to improve human health. Central storage units such as the Rutgers University Cell and DNA Repository (RUCDR) help investigators nationwide share data and biological specimens. To address space shortages and infrastructural needs and to broaden the scope of the molecular biology services, RUCDR has been awarded $9.5 million to renovate their biology laboratory. RUCDR's services provide approximately 90 NIH-funded grantees with resources that aid research in disease areas, including autism, schizophrenia, bipolar disorder and kidney diseases.

Researchers share insights into RNA

Tue, 11 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) LA JOLLA, Calif., May 11, 2010 -- Investigators from around the country came to Sanford-Burnham Medical Research Institute (Sanford-Burnham) on Friday, May 7, to share their knowledge of the burgeoning young field of microRNAs. These small non-coding nucleic acids turn off proteins and have been implicated in viral infection, cancer, cardiovascular disease, HIV and numerous other conditions.

The discovery that small RNAs could shut down gene expression was revolutionary, said Tariq Rana, Ph.D., who directs the RNA Biology program at Sanford-Burnham. Dr. Rana organized the symposium with Sanford-Burnham colleagues Rolf Bodmer, Ph.D., and Sumit Chanda, Ph.D.

The symposium, entitled RNAi and microRNA Regulatory Functions, featured a who's who of RNA biologists sharing their understanding of how these small RNAs regulate gene function and contribute to disease.

One of the speakers, Shiv Grewal, Ph.D., senior investigator at the National Cancer Institute, works to understand how RNAi regulates chromatin, the combination of proteins and DNA that makes up chromosomes. Dr. Grewal's research has shown that RNAi machinery stabilizes these critical structures. If you disrupt this process, chromosomes will not segregate properly, said Dr. Grewal. After cell division, one cell will get more and the other will get less, a very common feature in cancer cells.

Deepak Srivastava, M.D., a pediatric cardiologist and director of the Gladstone Institute of Cardiovascular Disease, has been working to understand how the heart develops. His research has shown that microRNAs and proteins work in complementary networks to help progenitor cells choose what kind of heart cells to become. There is a transcriptional network that controls cell fate decisions in the heart, said Dr. Srivastava. Overlaid on that is a translational network controlled by microRNAs that controls how much protein is made of those same transcription factors. But also, those transcription factors control the dose of microRNAs. It's a very coordinated network.

Amy Pasquinelli, Ph.D., associate professor at UC, San Diego, is working to determine how microRNAs bind to their target. We want to understand the pairing rules, said Dr. Pasquinelli. If we can understand those, we can use bioinformatics to predict, simply by looking at the microRNA sequence, where it's going to bind, what gene it will target and what will be the ultimate result.

Other researchers shared their work on a number of topics, including the fundamental roles of microRNAs in biology and epigenetics; developing cutting-edge technologies that use small RNAs to investigate disease processes; high-resolution structures of RNAi machinery; RNA-mediated regulation of herpes infections; and RNA-based treatments for neurodegenerative disorders, AIDS, cancer and metabolic diseases.

LA BioMed to receive $9.7 million stimulus grant for new research center

Thu, 08 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) LOS ANGELES (April 8, 2010) With a goal of creating jobs and enhancing chronic disease studies, the federal government is awarding a $9.7 million grant of stimulus funds to the Los Angeles Biomedical Research Institute (LA BioMed) for the construction of a new Chronic Disease Clinical Research Center on its campus, David I. Meyer, PhD, the institute's president and CEO, announced today.

Construction of the new research center is expected to create up to 190 new jobs and a new environment for LA BioMed's research into chronic obstructive pulmonary disease (COPD) and other respiratory ailments, cardiac disease and HIV/AIDS.

With the construction of a new research center, our distinguished investigators who study chronic diseases will be able to expand and strengthen their clinical research activities to provide promising new treatments and therapies to the underserved, Dr. Meyer said. There was incredibly stiff competition for the facilities grants, and it is a credit to LA BioMed's investigators and staff that the institute was able to secure a share of this one-time infusion of capital funding.

The grant comes from the National Institutes of Health National Center for Research Resources and is part of the American Recovery and Reinvestment Act, or the stimulus program. It requires rapid deployment of shovel-ready projects to ensure the grant creates jobs and stimulates the economy.

It is great news for Californians that LA BioMed received millions in stimulus dollars which will help it maintain essential services, save lives and provide comfort and care to people across the state, said California Governor Arnold Schwarzenegger. This much-needed funding will create jobs and build a state-of-the-art facility that will help researchers find cures and develop treatments for chronic diseases.

The construction of the new Chronic Disease Clinical Research Center is expected to generate 150 new construction-related jobs, and the expansion of research at LA BioMed is estimated to create up to 40 additional new jobs.

One-hundred fifty new construction jobs and up to 40 new staff positions at LA BioMed are a shot in the arm for the South Bay's economy, said U.S. Rep. Jane Harman, D-Venice. The grant will also foster the development of new treatments and therapies for chronic ailments. Congratulations to the doctors and researchers whose innovation and hard work will help save lives.

The grant will pay for the construction of a two-story, 23,171-square-foot research center that will consolidate the collaborative research programs of investigator groups who are studying chronic diseases. It will serve as the new home for LA BioMed's Center for Rehabilitative Medicine, its Center for Atherosclerosis Research, the HIV/AIDS research program and the Investigational Drug Service.

This grant award is great news for LA BioMed and the South Bay because it will create much-needed new jobs and help stimulate our local economy, said Los Angeles County Supervisor Mark Ridley-Thomas. LA BioMed is a pioneer in research that benefits the underserved in our society, and it is leading the way in turning great science into great medicine. I look forward to the advances in treatments and therapies that will be developed at LA BioMed's new Chronic Diseases Clinical Research Center.

The new Chronic Disease Clinical Research Center is scheduled to be completed by the fall of 2013, and it will include an outpatient research clinic, research pharmacy, office space, a cardiac CT reading center and exercise physiology, pulmonary function and cardiac labs.

This grant is great news for LA BioMed, for the South Bay and for anyone suffering from a chronic disease, said Los Angeles County Supervisor Don Knabe. LA BioMed is one of Los Angeles' real gems. Its physician-researchers take the knowledge they gain at the bedside of their patients into the labs where they develop therapies and treatments that will improve the lives of people around the globe. We are fortunate to have such an outstanding research facility located in the heart of the South Bay.

Think again about keeping little ones so squeaky clean

Tue, 08 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- A new Northwestern University study suggests that American parents should ease up on antibacterial soap and perhaps allow their little ones a romp or two in the mud --- or at least a much better acquaintance with everyday germs.

The study is the first to look at how microbial exposures early in life affect inflammatory processes related to diseases associated with aging in adulthood.

Most provocatively, the Northwestern study suggests that exposure to infectious microbes early in life may actually protect individuals from cardiovascular diseases that can lead to death as an adult.

Contrary to assumptions related to earlier studies, our research suggests that ultra-clean, ultra-hygienic environments early in life may contribute to higher levels of inflammation as an adult, which in turn increases risks for a wide range of diseases, said Thomas McDade, lead author of the study, associate professor of anthropology in Northwestern's Weinberg College of Arts and Sciences and a faculty fellow at the Institute for Policy Research.

Relatively speaking, humans only recently have lived in such hyper-hygienic environments, he stressed.

The research suggests that inflammatory systems may need a higher level of exposure to common everyday bacteria and microbes to guide their development. In other words, inflammatory networks may need the same type of microbial exposures early in life that have been part of the human environment for all of our evolutionary history to function optimally in adulthood, said McDade, also a member of Northwestern's Cells to Society (C2S).

The Northwestern study is the first research on microbial effects on inflammatory systems in infancy that relate in later life to diseases associated with aging. Advancing the scientific literature on the developmental origins of disease, the study arguably is the most significant research on long-term effects of early environments on human physiological function and health in adulthood.

The research took advantage of a longitudinal study of Filipinos, following participants in utero through 22 years of age, to get a better understanding of how environments early in life affect production of C-reactive protein (CRP) production in adulthood.

Levels of the protein rise in the blood due to inflammation, an integral part of the immune system's fight against infection. CRP research mostly has centered on the protein as a predictor of heart disease, independent of lipids, cholesterol and blood pressure, though researchers still dispute that association. Researchers have been looking at excess body fat as a primary source of pro-inflammatory cytokines that produce CRP and behavioral factors related to diet, exercise and smoking. And the CRP research largely has been conducted in relatively affluent settings, such as in the United States, with low levels of infectious diseases.

The Northwestern researchers were interested in what CRP production looks like in the Philippines, a population with a high level of infectious diseases in early childhood compared to Western countries. Relative to Western countries, the Philippines also has relatively low rates of obesity and cardiovascular diseases, consistent with the Northwestern research findings.

Blood tests showed that C-reactive protein was at least 80 percent lower for study participants in the Philippines when they reached young adulthood, relative to their American counterparts, though the Filipinos suffered from many more infectious diseases as infants and toddlers. Filipino participants in their early 20s had average CRP concentrations of .2 milligrams per liter -- five to seven times lower than average CRP levels for Americans. CRP concentrations for Americans in their early 20s were on average around 1 to 1.5 milligram per liter.

Early Origins of Inflammation: Microbial Exposures in Infancy Predict Lower Levels of C-reactive Protein in Adulthood, will be published online December 9 in the journal

HIV-related memory loss linked to Alzheimer's protein

Mon, 07 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) More than half of HIV patients experience memory problems and other cognitive impairments as they age, and doctors know little about the underlying causes. New research from Washington University School of Medicine in St. Louis suggests HIV-related cognitive deficits share a common link with Alzheimer's-related dementia: low levels of the protein amyloid beta in the spinal fluid.

However, by analyzing biomarkers in the fluid surrounding the brain and spinal cord, the researchers report Dec. 8 in the journal Neurology, they could distinguish patients with HIV-related cognitive impairments from patients with mild Alzheimer's disease. This is important because as patients with HIV age, some will develop cognitive deficits related to HIV and others to Alzheimer's. New Alzheimer's treatments in the pipeline to improve memory and thinking may not work for both conditions.

HIV patients with cognitive dysfunction don't have early Alzheimer's - although some of the symptoms may be similar, says lead author David Clifford, M.D., an authority on the neurological complications of HIV and director of Washington University's AIDS Clinical Trials Unit. The underlying biology of both conditions may be related to amyloid, and we think this clue can help us find the cause of cognitive impairment in HIV patients.

Cognitive dysfunction is a major problem among the estimated 1 million Americans living with HIV. The impairments are often mild but can affect a person's daily life, relationships and ability to hold a job. They include difficulties with memory, processing complex information and making decisions. These problems are expected to worsen as HIV patients live longer, due to potent drug cocktails that keep the virus in check.

In the new research, the scientists looked at the spinal fluid of 49 HIV patients with cognitive impairments, 21 HIV patients with normal cognitive function, 68 patients with mild Alzheimer's and 50 normal, healthy controls. The Alzheimer's patients were older (average age 74) than the controls (average age 50), impaired HIV patients (average age 48) and cognitively normal HIV patients (average age 43).

They tested the spinal fluid for the presence of amyloid beta - the protein that folds and accumulates in the brains of Alzheimer's patients and is thought to play a key role in driving the brain damage that characterizes the disease. They also looked at other biomarkers associated with Alzheimer's, including tau, a protein found in tangled nerve fibers in Alzheimer's patients.

When amyloid beta accumulates in the brains of Alzheimer's patients, levels decrease in the spinal fluid, and Clifford and his colleagues expected to find low levels of the protein in samples of the Alzheimer's patients they studied.

But they were surprised to find the same low levels in the spinal fluid of HIV patients with cognitive dysfunction. Both groups of patients had significantly lower amyloid beta levels than HIV patients without cognitive impairments and the normal controls. The lower levels are an indicator that amyloid beta in the brain alters the normal turnover of the protein in the body.

Although Australian and European researchers had uncovered a link between HIV-related cognitive deficits and amyloid beta in 2005 in a smaller study, Clifford thought that finding was an artifact and embarked on the current study largely to disprove it.

I really did not expect the biology of HIV cognitive dysfunction to be related to Alzheimer's, Clifford says. If you look at the brains of HIV patients with cognitive impairments, they don't look like Alzheimer's brains - they don't have the same atrophy or a plethora of plaques and tangles characteristic of Alzheimer's.

But low amyloid beta is where the similarity to Alzheimer's disease ends. The researchers found that patients with mild Alzheimer's had significantly higher levels of tau than either group of HIV patients or normal controls - a finding that strongly suggests Alzheimer's and HIV cognitive dysfunction are not one and the same, Clifford says.

He suspects the HIV-related cognitive impairment may be due to low levels of the virus that hide out in the brain, beyond the reach of drugs that can't easily cross the blood-brain barrier. Another cause may be low-grade inflammation in the brain that is driven by the virus.

Almost all HIV patients in the study were taking anti-retroviral therapy. I am almost certain the dementia in AIDS patients is linked to HIV and not to anti-retroviral drugs - we see it even in patients who haven't received HIV therapy, Clifford says. However, the more subtle impairment may be in some way associated with a change in the way the body processes amyloid beta. This will certainly be an important area of future research.

No-entry zones for AIDS virus

Thu, 12 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) The AIDS virus inserts its genetic material into the genome of the infected cell. Scientists of the German Cancer Research Center have now shown for the first time that the virus almost entirely spares particular sites in the human genetic material in this process. This finding may be useful for developing new, specific AIDS drugs.

Like all retroviruses, the AIDS virus (HIV) integrates its DNA into the genome of the infected cell. As integration sites, HIV usually prefers active genes that are transcribed frequently. This is advantageous for the virus, because this is where it finds large amounts of enzymes which are responsible for transcription. The virus abuses this cellular equipment for its own replication.

At DKFZ, Associate Professor (PD) Dr. Stephanie Laufs and Dr. Frank Giordano are trying to find out whether AIDS viruses can be used as gene delivery vehicles in gene therapy. Therefore, it is crucial for them to know where exactly HIV integrates into the genetic material of the host cell. This is a critical step in gene therapy, because depending on the position, this process can result in permanent activation of oncogenes or other damage. Therefore, the researchers took a very close look by starting an analysis of more than 46,000 known integration sites of HIV-based gene delivery vehicles that were determined in various gene therapy studies or are available in gene databases.

Up to now, researchers have been convinced that both HIV and HIV gene delivery vehicles have a particular preference for sites where gene transcription starts. At these sites there is an abundance of those enzymes which the viruses need. However, the database analysis produced an entirely different picture. While many HIV do really integrate close to transcription start sites, the investigators found hardly any such start points in the closest, immediate vicinity of the HIV integration sites, i.e. only 1,000 DNA building blocks to the left and to the right of them.

For the first time we have very precisely defined areas in the human genome where HIV hardly ever integrates, Giordano explains. The scientists are electrified by the result, because there must be a reason why HIV evades these sites. We assume that there is a particular mechanism at work which blocks the way for the virus, says Giordano. On the other hand, it is also possible that some factor that HIV needs for its integration is missing at these sites. The researchers even know already that this access barrier cannot be an unspecific one: Other retroviruses even prefer to insert their genetic material exactly at the transcription start sites, Laufs explains. Therefore, we assume that the mechanism protecting the transcription start sites of active genes from HIV genome integration very specifically prevents HIV integration. For example, this mechanism might block the work of an enzyme called integrase, which is responsible for integrating the viral DNA into the DNA of the infected cell.

This enzyme is currently in the focus of the search for an improved AIDS therapy. The highly active treatment available today attacks the virus from several different angles using different drugs: Reverse transcriptase inhibitors prevent the viral genome from being copied. Protease inhibitors block the maturation of new viral proteins. Scientists agree, however, that the best way of fighting the severe immune deficiency is to prevent integration of the viral genetic material into the DNA of the host cells. Substances preventing this, called integrase inhibitors, have been used in recent years, but the viruses have already started evading their effect through mutations. Therefore, virologists are urgently searching for new approaches to blocking this key enzyme of the virus. The mechanism that prevents HIV from integrating at the transcription start site might be a molecular model for developing such substances.

Indiana U. at APHA: Studies about why men and women use lubricants during sex

Mon, 09 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) An Indiana University study involving 2,453 women ages 18 to 68 found that lubricant use during sexual activity alone or with a partner contributed to higher ratings of pleasurable and satisfying sex.

Personal lubricants have long been recommended to women to improve the comfort of sexual intercourse and to reduce the risk of vaginal tearing, yet strikingly little available data is available on women's use of lubricants or associated vaginal symptoms.

The study, conducted by Debby Herbenick, associate director of the Center for Sexual Health Promotion at IU's School of Health, Physical Education and Recreation, involved women who used one of six different water- or silicone-based lubricants.

The study also found that side effects were rarely associated with lubricant use; vaginal tearing occurred during less than 1 percent of vaginal intercourse events and genital pain was reported in less than 5 percent of intercourse acts when lubricant was used.

Herbenick will present her findings at on Monday, Nov. 9, at 3:10 p.m. during the What's Sex Got To Do With It? session. Co-authors are Devon J. Hensel , IU School of Medicine; Kristen Jozkowski, Center for Sexual Health Promotion; Michael Reece, CSHP; and J. Dennis Fortenberry, IU School of Medicine.

Researchers from the Center of Sexual Health Promotion conducted more than 15 studies being presented at the APHA conference. Public health professionals routinely recommend the addition of lubricant to condoms during sexual activity, yet virtually no research has assessed the sexual situations during which the recommendations are followed. The following two CSHP studies help fill in the gaps.

A CSHP study involving 2,453 women examined their use of water-based or silicone-based lubricants during sexual activity. The use of lubricants during sexual activity has been recommended as a strategy to reduce the likelihood of vaginal tearing, which can increase risk for HIV and other STI. The study participants strongly endorsed the notion that lubricant use improved the sexual experience; in more than 70 percent of events, women indicated that using lubricants made sex feel very pleasurable and more comfortable (65.5 percent). The women in the study primarily were heterosexual (85.6 percent) and married (56.4 percent), with an average age of 32.5. Other findings: When applying lubricant, 58.4 percent of events involved application to the woman's genitals by their sexual partner, 54.7 percent involved women applying lubricant to their own or their partner's fingers, and 53.4 percent involved women applying lubricant directly on their partner's genitals. Most frequently reported reasons for lubricant use included the desire to reduce the risk of tearing (22 percent) and to make sex more comfortable (21.8 percent). Co-authors include lead author Jozkowski, Herbenick, Hensel, Reece and Fortenberry. The research was supported by The Patty Brisben Foundation. Jozkowski will present the findings on Monday, Nov. 9, at 2:30 p.m. during the Women and HIV: Emerging Issues session.

A CSHP study involving 1,834 men examined the use of lubricants during vaginal intercourse. The study involved 8,876 coital events, 46.8 percent of which involved the use of a latex condom and 24.7 percent of which involved the use of a lubricant. Additional results: most frequently, lubricant was added to the external tip of the condom after penile application (22.5 percent), directly in or around the partner's vagina (16.2 percent), and to both the condom and vagina (16.2 percent). The addition of lubricant to condoms was more likely during intercourse with a spouse than with a non-committed partner, during intercourse events of longer duration, when a female partner applied the condom to the partner's penis, and when a female partner used Nuva Ring, IUD or spermicidal jelly/foam as a method of contraception. The research was supported by The Patty Brisben Foundation. Co-authors include, Reece, Hensel, Herbenick, Fortenberry, and Brian Dodge, CSHP. Reece will present the findings on Monday, Nov. 9, at 10:30 a.m. during the Innovative Research on Sexual Health session.

Federal stimulus funds support studies geared to improving HIV care and prevention

Thu, 05 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) UCSF HIV researchers have received two NIH grants of $1 million each to study the use of web-based, patient controlled personal health records to improve health and HIV prevention outcomes for HIV positive patients.

Both studies are funded through the federal stimulus bill, The American Recovery and Reinvestment Act.

One study will look at using mobile phone text messages linked to a web-based personal health record to help HIV patients' adherence to pill-taking regimens.

Patients participating in the study will not only be assisted with taking their HIV medications, but also with medications for conditions like diabetes and hypertension. At least half the patients we see in our clinic have at least one other chronic disease that requires medication to control. Our hypothesis is that using individualized text message reminders linked to personal health records will help patients better succeed in self-management of their multiple health challenges, said James S. Kahn, MD, professor of clinical medicine at the UCSF Positive Health Program at San Francisco General Hospital.

Two methods will be used to assess adherence to medication regimens in this project. Self-report of pill taking is one. A biological marker, measurement of antiviral drug levels in hair, is the other method used. A member of the research team, UCSF assistant professor of medicine Monica Gandhi, MD, MPH, has shown this method to be a better correlate of success in HIV viral suppression during treatment than other variables usually considered.

The other study will test the feasibility and acceptability of a web-based strategy that seeks to reduce drug and alcohol use and accompanying HIV risk behaviors and improve antiretroviral medication adherence by HIV positive patients.

The strategy is called SBIRT and consists of screening for drug and alcohol use, a brief intervention and referral to treatment. It has been shown to be effective in many populations in reducing drug and alcohol use but has never been used in a HIV primary care setting. With several studies showing a relationship between high HIV transmission risk behaviors and drug and alcohol use, effective administration of the SBIRT strategy could also reduce HIV transmission according to the project team.

The project will compare SBIRT delivered through a self-administered and web-based method using patients' electronic health records with SBIRT delivered through a provider-administered protocol during clinic appointments using an electronic health record system.

We want to see if the SBIRT approach will work in this population and this setting to not only reduce drug and alcohol use but also succeed in reducing HIV transmission associated with substance use. We are hoping to find out whether patients are more open to responding to sensitive topics with a self-administered web-based approach than they are talking directly with their clinician, said Carol Dawson-Rose, PhD, MSN, RN, associate professor of nursing at the UCSF Center for AIDS Prevention Studies.

Both studies use HERO (Health Care Evaluation Record Organizer), a web-based electronic medical record system and research database developed by Kahn and T. Van Nunnery, a programmer/analyst at UCSF, and myHERO. Integrated with HERO, myHERO is a publicly-accessible personal health record enabling patients to access information online from their own medical record. This complete electronic health record system is secure, flexible, extensible, and is exportable to other clinical care venues.

Specialists in hearing, HIV come together to study AIDS patients

Tue, 03 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) Specialists in HIV and in hearing at the University of Rochester Medical Center are teaming up to measure the hearing of people with AIDS.

The five-year study is believed to be the first large study of its kind testing the hearing of people with HIV/AIDS and comparing the results with those from people without HIV. The new effort, supported by a $1.9 million grant from the National Institute on Deafness and Other Communication Disorders, is the result of collaboration between hearing experts and experts on HIV and AIDS.

The study is led by Amneris Luque, M.D., associate professor of Medicine and director of Strong Memorial Hospital's AIDS Clinic, which provides care for more than 900 patients. The project brings together experts in the nervous system and the immune system, both of which are involved in many types of hearing loss. The first of 360 participants who will take part in the study enrolled last week.

Luque will work closely with hearing researcher Robert Frisina, Ph.D., professor of Otolaryngology, Biomedical Engineering, and Neurobiology and Anatomy. Frisina's team, which is based at the Medical Center as well as the National Technical Institute for the Deaf, is widely regarded as one of the premier groups in the world looking at age-related hearing loss.

Luque says that since AIDS was recognized nearly three decades ago, hearing loss among some patients has been reported. However, these reports have been scattered and unconfirmed.

There has not been a systematic study looking at hearing function in people with HIV, said Luque. If there is hearing impairment, it could be related to the disease itself; it might be related to infections that our patients with AIDS are prone to getting; or it might be related to the medications used to treat the disease.

Luque notes that some scientists have found evidence that people with HIV/AIDS may be aging prematurely compared to people without HIV. The team will look closely at whether a similar acceleration of aging may play a role in the hearing of people with HIV.

In addition, of course, many people without HIV also experience hearing loss. Causes of hearing loss can include noise exposure, medications used to treat conditions like cancer or other infections, or heredity. Sorting out those causes from other processes unique to people with HIV is challenging.

We're trying to tease out what is happening in people with HIV, said Luque. Is there something inherent about the infection that may be involved in hearing loss?

Participants in the study will undergo periodic, rigorous testing of their hearing. Scientists will study patients at various stages of HIV infection, including some infected people known as long-term non-progressors or elite controllers, people in whom the infection hasn't advanced even without medication.

The team will compare the results in HIV/AIDS patients to results in healthy people who have had similar hearing tests conducted at the International Center for Hearing and Speech Research, where Frisina is associate director. That database includes extensive information about the hearing of more than 1,400 healthy people who have had similar testing done.

NIH launches 2009 H1N1 influenza vaccine trials in HIV-infected pregnant women

Fri, 09 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The first clinical trials to test whether the 2009 H1N1 influenza vaccine can safely elicit a protective immune response in pregnant women launched yesterday, and a trial to conduct the same test in HIV-infected children and youth will begin next week. The International Maternal Pediatric Adolescent AIDS Clinical Trials Group is conducting the studies, which are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of the National Institutes of Health.

These studies are important because HIV infection and pregnancy both increase the risk for a poor immune response to the normal 15-microgram dose of seasonal influenza vaccine given to the general population, says NIAID Director Anthony S. Fauci, M.D. Moreover, children, young people and pregnant women are at higher risk for more severe illness from the 2009 H1N1 influenza virus than other groups, and HIV-infected individuals in these populations may be particularly vulnerable.

Because of the increased vulnerability of these populations, these trials are testing whether doses of licensed 2009 H1N1 influenza vaccine that are higher than doses being tested in other groups can safely elicit protective immune responses in HIV-infected children, youth and pregnant women, adds Lynne Mofenson, M.D., chief of the Pediatric, Adolescent and Maternal AIDS Branch in NICHD.

One trial will enroll 130 HIV-infected pregnant women ages 18 to 39 years who are in their second or third trimester (14 to 34 weeks) of pregnancy. The other trial will enroll 140 children and youth aged 4 to 24 years who were infected with HIV at birth.

Thirty-five sites and eight sub-sites across the United States and Puerto Rico are eligible to conduct the trials. Each volunteer will receive two 30-microgram doses of 2009 H1N1 influenza vaccine 21 days apart. (In contrast, the NIAID studies of 2009 H1N1 influenza vaccine in HIV-uninfected children, youth and pregnant women are testing doses of 15 and 30 micrograms.)

Safety data will be collected and monitored closely by the study investigators and an independent safety monitoring committee. The strength and longevity of the immune response elicited by the vaccine will be gauged in several ways.

The study team will take blood samples from the pregnant women after each dose and three and six months after delivery to measure the concentration of antibodies the women produce against 2009 H1N1 influenza virus and how strong that antibody response remains over time. After the women give birth, study staff will sample umbilical cord blood to measure the concentration of maternal antibodies against the H1N1 virus that were transferred to the infants through the placenta. The study team also will collect small blood samples from the infants at 3 and 6 months of age to measure their level of maternally derived antibody protection from the virus over time. The infants will not receive vaccine.

Similarly, in children and young people, the strength and longevity of the immune response will be gauged by testing blood samples taken 21 days after the first dose, 10 days after the second dose, and six months after entering the study.

The vaccine, manufactured by Novartis Vaccines and Diagnostics, contains inactivated 2009 H1N1 influenza virus, so it is impossible to become infected with the virus by receiving the vaccine. The vaccine does not contain adjuvant, a substance added to some vaccines to improve the body's response to vaccine.

Research on seasonal influenza vaccine and vaccines for other diseases in HIV-infected and other populations suggest that higher doses of vaccine tend to elicit stronger immune responses. These stronger responses, in turn, increase the concentration of protective antibodies in the bloodstream, which likely is beneficial to both the vaccinated individual and, if pregnant, to her fetus. This is the rationale for testing whether higher doses of licensed 2009 H1N1 influenza vaccine elicit a protective immune response in HIV-infected individuals and whether that protection is transferred to the fetuses of vaccinated pregnant women.

HIV vaccine regimen demonstrates modest preventive effect in Thailand clinical study

Thu, 24 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) In an encouraging development, an investigational vaccine regimen has been shown to be well-tolerated and to have a modest effect in preventing HIV infection in a clinical trial involving more than 16,000 adult participants in Thailand. Following a final analysis of the trial data, the Surgeon General of the U.S. Army, the trial sponsor, announced today that the prime-boost investigational vaccine regimen was safe and 31 percent effective in preventing HIV infection.

These new findings represent an important step forward in HIV vaccine research, says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, which provided major funding and other support for the study. For the first time, an investigational HIV vaccine has demonstrated some ability to prevent HIV infection among vaccinated individuals. Additional research is needed to better understand how this vaccine regimen reduced the risk of HIV infection, but certainly this is an encouraging advance for the HIV vaccine field.

We thank the trial staff in Thailand and the United States for their years of effort in successfully conducting this study and the study participants and the people of Thailand for their long-standing support of HIV vaccine research, Dr. Fauci adds.

The Thai Phase III HIV vaccine study, also known as RV144, opened in October 2003. The placebo-controlled trial tested the safety and effectiveness of a prime-boost regimen of two vaccines: ALVAC-HIV vaccine (the primer dose), a modified canarypox vaccine developed by Sanofi Pasteur, based in Lyon, France, and AIDSVAX B/E vaccine (the booster dose), a glycoprotein 120 vaccine developed by Vaxgen Inc., and now licensed to Global Solutions for Infectious Diseases (GSID), based in South San Francisco, Calif. The vaccines are based on the subtype B and E HIV strains that commonly circulate in Thailand. The subtype B HIV strain is the one most commonly found in the United States.

Led by principal investigator Supachai Rerks-Ngarm, M.D., of the Thai Ministry of Public Health's Department of Disease Control, the study was sponsored by the U.S. Army in collaboration with NIAID, Sanofi Pasteur and GSID. The trial, conducted in the Rayong and Chon Buri provinces of Thailand, enrolled 16,402 men and women ages 18 to 30 years old at various levels of risk for HIV infection. Study participants received the ALVAC HIV vaccine or placebo at enrollment and again after 1 month, 3 months, and 6 months. The AIDSVAX B/E vaccine or placebo was given to participants at 3 and 6 months. Participants were tested for HIV infection every 6 months for 3 years. During each clinic visit, they were counseled on how to avoid becoming infected with HIV.

In the final analysis, 74 of 8,198 placebo recipients became infected with HIV compared with 51 of 8,197 participants who received the vaccine regimen. This level of effectiveness in preventing HIV infection was found to be statistically significant. The vaccine regimen had no effect, however, on the amount of virus in the blood of volunteers who acquired HIV infection during the study.

The Thai study demonstrates why the HIV vaccine field must take a balanced approach to conducting both the basic research needed to discover and design new HIV vaccines and, when appropriate, testing candidate vaccines in people, says Margaret I. Johnston, Ph.D., director of NIAID's Vaccine Research Program within the Division of AIDS. Both avenues provide critical information that will continue to help us better understand what is needed to develop a fully protective HIV vaccine.

NIAID and the collaborating partners are working with other scientific experts to determine next steps, including additional research of the RV144 vaccine regimen and the need to consider the impact of these new findings on other HIV vaccine candidates.

Individuals who acquired HIV infection while participating in the Thai trial have been provided access to HIV care and treatment, including highly active antiretroviral therapy based on the guidelines of the Thai Ministry of Public Health.

Clinical trial of antiretroviral-based HIV prevention strategies for women now under way

Wed, 16 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A new, large-scale clinical trial is examining whether antiretroviral medications normally used to treat HIV infection can also prevent HIV infection in women when applied as a vaginal gel or taken as oral tablets once daily.

The study, called Vaginal and Oral Interventions to Control the Epidemic (VOICE) or MTN-003, will involve up to 5,000 HIV-uninfected women at risk for HIV infection in four African countries. The trial will test the safety and efficacy of two different HIV prevention strategies: an investigational microbicide gel containing the antiretroviral drug tenofovir, and oral tablets containing tenofovir or a combination of tenofovir and emtricitabine known by the brand name Truvada. The tablets would be taken prior to exposure in an approach known as pre-exposure prophylaxis, or PrEP. Testing a microbicide and PrEP in the same trial will enable scientists to directly compare the two strategies in terms of their safety and acceptability.

Notably, the VOICE study is the first efficacy study of an investigational microbicide in which participants apply the gel once daily rather than shortly before sexual intercourse. If found effective, this approach would allow participants to choose whether to use the gel in association with sexual activity or at another time of day, permitting greater privacy and convenience of use.

We need multiple, scientifically proven HIV prevention strategies acceptable to different populations to effectively combat the spread of the virus, and PrEP and microbicides are two promising approaches that we are actively pursuing, says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). The VOICE study is designed to answer multiple crucial questions about these experimental interventions, with an emphasis on protecting women from HIV.

NIAID is sponsoring and funding the trial with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the National Institutes of Health. Co-sponsors are Gilead Sciences Inc. of Foster City, Calif., and CONRAD of Arlington, Va. The NIH-funded Microbicide Trials Network is conducting the study.

Women make up half of all people worldwide living with HIV, and in sub-Saharan Africa, women represent nearly 60 percent of adults living with the virus. In most cases, women become infected with HIV through sexual intercourse with an infected male partner. An effective microbicide or PrEP regimen could give women an HIV prevention method they control. This would be particularly helpful in situations where it is difficult or impossible for women to refuse sex or negotiate condom use with their male partners.

The VOICE study is being conducted at 14 sites in South Africa, Uganda, Zambia and Zimbabwe. The Phase IIb study, which will last approximately three and a half years, is being led by Zvavahera Mike Chirenje, M.D., of the University of Zimbabwe in Harare, and Jeanne Marrazzo, M.D., M.P.H., of the University of Washington in Seattle. The sexually active, HIV-uninfected women ages 18 to 45 participating in the study will be randomly assigned to one of five regimens, each performed once daily:

ART therapy for babies, mothers safely reduces HIV transmission

Wed, 22 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Giving daily antiretroviral syrup to breastfeeding infants or treating their HIV-infected mothers with highly active antiretroviral drugs is safe and effective in preventing mother-to-child HIV transmission through breast milk, a study led by University of North Carolina at Chapel Hill investigators has found.

This is an exciting development, said Charles van der Horst, M.D., a professor in the UNC School of Medicine and the study's lead investigator. We may be able to spare mothers in the developing world a horrible choice by offering them an effective method for preventing transmission of HIV during breastfeeding.

These findings, from investigators at UNC-Chapel Hill, UNC Project-Malawi in Lilongwe, Malawi and the U.S. Centers for Disease Control and Prevention (CDC), were presented July 22 at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, South Africa (Abstract .WELBC1 - Late Breaker C 16:30 - 17:30 Session Room 2).

Approximately 420,000 infants are infected with HIV annually, half through breast milk. HIV-infected women in resource-constrained areas face a terrible dilemma: provide the many health and nutritional benefits of breast milk but face a 20 percent chance of transmitting the virus to their baby or choose costly formula, which relies on an unsafe water supply and carries a higher risk of morbidity and mortality, and avoid transmitting HIV.

The Breastfeeding, Antiretrovirals and Nutrition (BAN) study is the only large-scale, randomized trial comparing infant prophylaxis or maternal treatment to an enhanced standard-of-care arm in the prevention of HIV transmission through breast milk. The study was conducted in Lilongwe, Malawi at a single site. Investigators randomly assigned at total of 2,367 mother-infant pairs to one of three treatment arms. For both the interventions, the probability of HIV-infection was significantly lower than in the enhanced control arm.

Of the randomized infants, 4.9 percent were found to be HIV positive at birth. Among infants who were HIV-free at one week old, 6.4 percent on the enhanced control arm were infected by 28 weeks, compared to 3.0 percent of the infants on the maternal treatment arm and 1.8 percent of the infants who received daily nevirapine syrup. Upon examining the probability of HIV infection or death by 28 weeks postpartum, 7.6 percent of the infants on the enhanced control arm were HIV-infected or died compared to 4.7 percent of the infants on the maternal treatment arm, and 2.9 percent of the infants on the infant prophylaxis arm.

The BAN study results give global and national policy makers the choice of which intervention (maternal or infant antiretroviral intervention) to implement based on the conditions and resources in their particular setting. We hope to see these results translated quickly into program and policy.

New method for HIV testing holds promise for developing world

Tue, 21 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, NC -- A new technique that detects the HIV virus early and monitors its development without requiring refrigeration may make AIDS testing more accessible in sub-Saharan Africa.

According to UNAIDS, sub-Saharan Africa accounts for almost a third of all new HIV infections and AIDS-related deaths globally. Yet there may be many people who do not get tested due to the high cost of treatment and minimal access to health care.

Duke Physician John Crump and a team of researchers recently completed a 10-month experiment at two remote sites in Tanzania. They examined Tanzanian infants born to HIV-infected parents and people with known HIV infections who needed monitoring of their viral loads. Viral load is a measurement used to diagnose HIV infection or determine the severity of HIV infection.

In the largest field study of its kind, researchers compared viral load measurements by using the current standard of frozen plasma and the alternative method of dried blood spots (DBS). The samples were measured at a central lab at the Kilimanjaro Christian Medical Centre in Moshi, some 250 and 350 kilometers away from the two study sites.

The Duke study found a strong correlation between viral load values in plasma and DBS, making the two testing approaches comparable. This finding could lay the foundation for a new way of testing for and monitoring patients with HIV in the future, according to Dr. John Bartlett, Duke Global Health Institute Associate Director for Research.

The sooner infants are diagnosed with HIV, the sooner they can receive life-prolonging medications to treat the disease. The infection cannot be detected in newborns using the typical HIV antibody test, and must be detected with other techniques, including viral load testing.

Viral load testing is also the optimal way for monitoring HIV infection in patients with known infections, especially for those receiving treatment.

But few labs in Tanzania perform the viral load procedure, and blood samples must be transported long distances to specialized medical facilities for testing. Plasma requires continuous cold storage during shipment, which can be challenging or impossible in resource-limited settings. This may prevent people from getting tested or result in inaccurate tests.

Dried blood spots offer the advantage of not requiring cold storage, says Bartlett, who also points out that this method may result in lower total health care costs. Before using it for care and treatment programs, it will need further evaluation. But, this is the largest field study of DBS's done to date, and the results appear promising.

Treatment with highly active antiretroviral therapy for HIV helps control Hepatitis B

Wed, 15 Jul 2009 14:12:37 PST

( from http://www.rxpgnews.com ) Prolonged use of highly active antiretroviral therapy (HAART) to treat people infected with both HIV and hepatitis B (HBV) helps to better control the hepatitis B infection and could delay or prevent liver complications, according to a new study by researchers at Wake Forest University School of Medicine.

Researchers also found that patients who had higher levels of a common liver enzyme upon beginning treatment for HIV-HBV co-infection were at an increased risk of being diagnosed with cirrhosis within the first few years of follow-up. Cirrhosis is a disease that scars the liver, progressively shutting it down. The enzyme is one released into the bloodstream after liver damage.

"One of the most interesting findings was the confirmation that a simple marker, such as transaminase levels before treatment, is useful in identifying patients at higher risk of developing HBV-related complications in a few years," said lead researcher Marina Núñez, M.D., Ph.D., an assistant professor in the Section on Infectious Diseases, in the Department of Internal Medicine at the School of Medicine.

The study is appears in the May/June issue of HIV Clinical Trials, published today.

HBV is a contagious liver disease, contracted in the same way as HIV – through intravenous drug use, sexual contact or mother-to-newborn transmission. Left untreated, it can lead to fatal liver disease or liver cancer.

HIV increases the activity of HBV, speeds the progression of related liver disease and might decrease the effectiveness of treatments for HBV.

But Núñez and Tsan Lee, a medical student at the School of Medicine, found that prolonged use of highly active antiretroviral therapy, including one or more drugs active against HBV, can lead to clearance of the HBV infection in co-infected patients. HAART is the treatment for HIV infection, consisting of a combination of drugs commonly known as the "cocktail."

For the study, researchers reviewed medical records of patients seen in an adult HIV clinic between 1990 and 2008. They included in the study all patients with positive HIV antibody, hepatitis B and at least three months of follow-up care on record.

Of the 72 patient charts reviewed – primarily black males with a median age of 39 and advanced HIV disease at the time of diagnosis – 64 of the patients received HAART that included drugs effective in treating HBV, for a median duration of one year. The researchers were looking for whether the patients were diagnosed with liver complications such as cirrhosis and liver cancer over the course of treatment, and whether the chronic HBV infection improved.

Analysis showed that receiving HAART combined with HBV treatment for a longer period of time was significantly associated with reduced and, in some cases cleared, chronic HBV infection.

Núñez said these findings "stress the importance of good control of the HIV and HBV infections through maintained compliance with HAART including drugs to treat HBV.

"In HBV-HIV patients with the elevated enzyme levels that signal liver damage, it is even more important to control the HBV infection in an attempt to decrease the risks of complications. Those patients should also be more closely screened for liver complications."

Probiotics can increase effectiveness of some antibiotic therapies

Thu, 09 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Antimicrobial treatments for bacterial vaginosis (BV) are effective, but taking lactobacillus tablets alongside metronidazole antibiotic therapy increases effectiveness over taking this antibiotic alone, according to a Cochrane Systematic Review. The researchers also concluded that intravaginal lactobacillus was as effective as oral metronidazole, although they did note unexplained drop-outs from the trials.

BV is a very common vaginal infection. Traditionally, antibiotics in tablet or gel form have been given to treat the disease, but some have unpleasant side effects. BV is usually a mild disease and can pass unnoticed but is associated with an increased risk of HIV transmission.

Treating BV could help reduce susceptibility of women to HIV. Therefore it is important, particularly in the developing world, to establish the most effective and appropriate forms of treatment, says lead researcher Oyinlola Oduyebo, of the Department of Medical Microbiology and Parasitology at the University of Lagos in Lagos Nigeria.

The researchers reviewed 24 trials involving 4,422 people. The antibiotics clindamycin and metronidazole both cured BV in over 90% of cases within two to three weeks, although there was a high rate of relapse. Side effects of metronidazole included nausea and a metallic taste in the mouth. However, it is the cheaper option and therefore likely to remain the most widely used in developing countries. Lactobacillus probiotic taken alongside metronidazole and taken intravaginally both showed significant effectiveness. Hydrogen peroxide and triple sulphonamide cream were not effective.

There are a range of good treatments for BV, but the high relapse rates require more attention and indicate that we need more research into other agents that can increase their effectiveness, said Oduyebo. We also need to understand why so many people dropped out of the Lactobacillus trials as this suggests there are unreported adverse effects.

Indian American helps design vaginal ring to prevent HIV transmission

Thu, 18 Jun 2009 12:27:59 PST

( from http://www.rxpgnews.com ) An Indian American endocrinologist has helped develop a vaginal ring that would prevent conception and transmission of HIV infection, by releasing multiple types of non-hormonal agents and microbicides.

Worldwide, there are about five million new infections and three million deaths every year caused by HIV/AIDS alone.

If proven successful in future clinical trials, the vaginal ring could empower women to protect themselves from unintended pregnancy and sexually transmitted diseases.

The ring may also someday represent a novel method to prevent STDs for those with aversion to currently available methods, with hormonally derived active agents, or with allergies to latex condoms.

'This device is a new approach to birth control, because it avoids the long-term use of hormonal methods that have been associated with increased risk of certain cancers,' said Brij Saxena, study co-author and professor of reproductive biology and endocrinology at Weill Cornell Medical College -.

'At the same time, this is the first device to simultaneously offer the possibility to prevent unintended pregnancy and HIV transmission,' said Saxena, who did his B.Sc, M.Sc and Ph.D from Lucknow University - in 1949, 1951 and 1954, respectively.

'No one has ever conquered a viral epidemic with treatment, so prevention is the most effective option. Ideally, an HIV vaccine is the most desirable method, but that is not foreseeable in the near future,' explained Jeffrey Laurence, study co-author and physician at New York-Presbyterian Hospital/WCMC.

'The next best thing would be something that would prevent infection and put the power in the susceptible female partner's control. That's the potential a device such as this can offer.'

The vaginally inserted ring is incorporated with multiple antiviral drugs that prevent HIV infection and are time-released over a period up to 28 days, said a WCMC release.

'The compounds in the device are natural materials that are already approved by the US Food and Drug Administration for use in humans,' explained Saxena.

The results were published recently in AIDS.

One step closer to the HIV vaccine

Sun, 17 May 2009 11:05:52 PST

( from http://www.rxpgnews.com ) A research team may have broken the stubborn impasse that has frustrated the invention of an effective HIV vaccine, by using an approach that bypasses the usual path followed by vaccine developers. By using gene transfer technology that produces molecules that block infection, the scientists protected monkeys from infection by a virus closely related to HIV—the simian immunodeficiency virus, or SIV—that causes AIDS in rhesus monkeys.

"We used a leapfrog strategy, bypassing the natural immune system response that was the target of all previous HIV and SIV vaccine candidates," said study leader Philip R. Johnson, M.D., chief scientific officer at The Children's Hospital of Philadelphia. Johnson developed the novel approach over a ten-year period, collaborating with K. Reed Clark, Ph.D., a molecular virologist at Nationwide Children's Hospital in Columbus, Ohio.

The study appeared today in the online version of Nature Medicine.

Johnson cautioned that many hurdles remain before the technique used in this animal study might be translated into an HIV vaccine for humans. If the technique leads to an effective HIV vaccine, such a vaccine may be years away from realization.

Most attempts at developing an HIV vaccine have used substances aimed at stimulating the body's immune system to produce antibodies or killer cells that would eliminate the virus before or after it infected cells in the body. However, clinical trials have been disappointing. HIV vaccines have not elicited protective immune responses, just as the body fails on its own to produce an effective response against HIV during natural HIV infection.

The approach taken in the current study was divided into two phases. In the first phase, the research team created antibody-like proteins (called immunoadhesins) that were specifically designed to bind to SIV and block it from infecting cells. Once proven to work against SIV in the laboratory, DNA representing SIV-specific immunoadhesins was engineered into a carrier virus designed to deliver the DNA to monkeys. The researchers chose adeno-associated virus (AAV) as the carrier virus because it is a very effective way to insert DNA into the cells of a monkey or human.

In the second part of the study, the team injected AAV carriers into the muscles of monkeys, where the imported DNA produced immunoadhesins that entered the blood circulation. One month after administration of the AAV carriers, the immunized monkeys were injected with live, AIDS-causing SIV. The majority of the immunized monkeys were completely protected from SIV infection, and all were protected from AIDS. In contrast, a group of unimmunized monkeys were all infected by SIV, and two-thirds died of AIDS complications. High concentrations of the SIV-specific immunoadhesins remained in the blood for over a year.

Further studies need to be conducted if this technique is to become an actual preventive measure against HIV infection in people, Johnson said. "To ultimately succeed, more and better molecules that work against HIV, including human monoclonal antibodies, will be needed," he and his co-authors conclude. Finally, added Johnson, their approach may also have potential use in preventing other infectious diseases, such as malaria.

Humanized mouse infected with HIV vaginally and rectally allows testing

Sun, 19 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The humanized mouse developed by Dr. J. Victor Garcia-Martinez has allowed the University of Texas Southwestern physician-scientist to conduct HIV/AIDS studies that would have been impossible without such a small animal model of HIV infection. The virus only infects humans and chimpanzees, which are protected as endangered species.

But because the new mouse model is a chimera, with a human immune system, it can be infected. Last year, using these humanized mice, a team of scientists led by Dr. Garcia-Martinez demonstrated that antiretroviral drugs given before and after exposure to HIV could prevent vaginal transmission of the virus. That suggests the possibility that women at high risk of HIV infection might one day be able to take a pill on a regular basis. And, since the drugs tested are already available, having gone through the long and complex approval process, that day might be sooner rather than later.

On Sunday, April 19, Dr. Garcia-Martinez tells fellow scientists attending Experimental Biology 2009 in New Orleans that the team is now using the mouse model to obtain evidence that these same approaches apply to protecting men.

Dr. Garcia-Martinez's presentation, updating improvements in the humanized mouse and in the progress of this and other work using the mouse model of human HIV/AIDS infection, is part of the scientific program of the American Society for Biochemistry and Molecular Biology.

First created in 2006, by Dr. Garcia and colleagues at UT Southwestern and the University of Minnesota, the humanized mouse used in these studies represented a new frontier in the preclinical testing of experimental drugs. Early mice models of disease were created by breeding mice that were immunodeficient in order that they would not reject grafts of human tissue. The big advance in the mouse created by Dr. Garcia-Martinez's group is that the mouse develops a human immune system, thanks to transfer of fetal human liver and thymic tissue cells that repopulate the bone marrow, which produces more cells.

The problem with using animals other than humans and chimpanzees for HIV/AIDS studies had been that the other animals, including ordinary mice, never become infected even when exposed to massive amounts of the virus. But the Garcia-Martinez mouse model (called BLT for bone marrow-liver-thymus) can easily be infected with HIV by both rectal and vaginal transmission, since both areas of the mouse body contain human cells.

With a long term-goal to investigate novel approaches to prevent HIV transmission, the team began with male to female infection. Women are at higher risk of infection during heterosexual sex with an infected partner, and women worldwide account for more than half of the estimated 11,000 newly acquired infections every day, with a majority of those transmissions occurring via the vaginal route. However, says Dr. Garcia-Martinez, male to male sexual contact accounts for a high proportion of the HIV/AIDS cases in the United States and rates of such transmission continue to rise, despite extensive educational campaigns.

Dr. Garcia-Martinez believes these statistics clearly reflect an urgent need to devise and implement potential interventions that could prevent both vaginal and rectal HIV-1 transmission especially among high-risk populations. The humanized mouse model provides an increasingly effective tool to move in that direction.

Education slowing AIDS in sub-Saharan Africa

Sun, 22 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Increased schooling across sub-Saharan Africa may be lowering new HIV infections among younger adults, according to sociologists, suggesting a shift in a decades-long trend where formal education is considered an AIDS risk factor.

While education in general has a positive impact on global public health, when it comes to HIV and AIDS in sub-Saharan Africa, education has had a completely opposite effect.

During the early stages of the HIV pandemic in the region, the disease passed unnoticed amidst the onslaught of other infections. When scientists took a closer look at the deadly new disease, they found that more often males with a higher than average education were contracting the disease.

Before the 1990s, in the impoverished regions of sub-Saharan Africa, even modest amounts of education afforded males higher income, more leisure time, and, for some males, greater access to commercial sex workers, explained David Baker, professor of education and sociology at Penn State and lead author of the study. HIV-infected higher-status males then spread the infection to both educated and uneducated women, which moved the disease into the general population.

Baker and his Penn State colleagues John Collins and Juan Leon, both graduate students, believe that information about AIDS that was already percolating in wealthier countries did not get to sub-Saharan Africa until the mid 1990s. AIDS was seen as a homosexual, urban disease and either neglect or active misinformation campaigns in some African countries ensured that the preventative effects of education never took root. But among younger people in the region, formal education is emerging as a major preventative factor against new infections. They report their findings in the current issue of the UNESCO journal Prospects.

There needs to be a very clear message, both to the donor community and to governments in sub-Saharan Africa, that expanding quality primary schools has to be a topmost priority, said Collins, co-author of the study. It will not only have economic benefits, but also health benefits.

To find what has happened recently to the link between formal education and HIV infections, the researchers analyzed data from surveys previously undertaken in 11 countries across the region between 2003 and 2005. They specifically looked at males ages 15 to 24, 25 to 34, and older than 35.

Survey participants were tested for HIV infection and interviewed about their education, social status, and sexual behavior.

The researchers argued that because the youngest members of the oldest group -- the 35 and older -- became sexually mature in the late 1980s, when there was little or no information about AIDS, higher education would show as a risk factor instead of a social vaccine.

Statistical analyses of the data suggest that in all 11 countries formal education had no effect on HIV infections in the oldest group, probably because many older adults, educated and uneducated have already been exposed to the virus and many have died. However, having some schooling did reduce the risk of HIV infections in the youngest group by up to 34 percent in Guinea, Malawi, Senegal, Cameroon, Ghana, and Kenya.

At 24 years, the oldest member of this young group reached sexual maturity in the mid 1990s, when there was already widespread knowledge that HIV and AIDS could be contracted through unprotected sex and intravenous drug use, explained Baker.

The researchers hypothesize that, reasoning skills gained in school by younger adults play a preventative role against HIV in sub-Saharan Africa.

More educated people have the cognitive tools to make better sense out of facts presented to them, explained Baker. We have shown that when there is sufficient information, and no misinformation, people with education adopt healthy strategies to avoid infections.

The Penn State researchers caution that while a large number of deaths in the early stages of the HIV pandemic could mask the true effects of education in the oldest group, the findings hold key policy implications for turning education into a social vaccine against HIV in sub-Saharan Africa.

According to Baker, AIDS is a complicated disease and it can only be tackled effectively by providing people with an everyday, accurate working theory of how the disease is transmitted. We are telling the governments that increased literacy is an explicit prevention strategy against HIV because it will help stop pandemics, he said.

The Penn State researcher also asks non-governmental organizations to reevaluate their educational programs.

The kind of information being supplied by NGOs is scandalous because it is so simplistic and minimalist, particularly for low-educated people, that they are not going to figure this disease out in time to prevent their own infection, Baker added.

UCSF Transgender HIV Prevention Center funded to provide primary care information

Thu, 12 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The UCSF Center of Excellence for Transgender HIV Prevention (CoE) has received a grant from The California Endowment that will expand access to information and resources on providing culturally competent health care to trangender individuals.

Many physicians are in dire need of the information that we will make available in order to provide the highest quality and most appropriate healthcare to transpeople. This grant will improve the quality of medical care received by transpeople in California and around the nation, said UCSF CoE director, JoAnne Keatley, MSW.

In addition, this grant brings the CoE into the healthcare arena and takes us closer to our vision of becoming a comprehensive center for transgender health, added Keatley.

The CoE was launched in 2007 to provide leadership, capacity building, professional training, policy advocacy, research development, and resources to increase access to culturally competent HIV prevention services for transgender people in California.

The establishment of the Center of Excellence in Transgender HIV Prevention was a historic event. This is the first time any state has funded a statewide effort to impact HIV among transpeople, the launching of the website provides access to the resources and information that providers need in order to deliver culturally competent, effective services, said Keatley.

The transgender community is currently experiencing the highest rates of HIV in many parts of California. In Los Angeles, studies have shown that between one quarter and one half of trans women in the county are living with HIV. In San Francisco, the percentage of trans women living with HIV is estimated to be between 16 and 60 percent. In San Diego, 15 percent of trans women are estimated to be HIV positive. And in one study in Alameda County, it was reported that 58 percent of the African American trans women who participated in the study were living with HIV.

The CoE receives funding from the California Department of Public Health, Office of AIDS.

Access to appropriate and sensitive primary health care is an important component of HIV prevention for transgender individuals, said Michelle Roland, MD, division chief of the Office of AIDS. The California Endowment's grant to expand access to transgender primary care information is an important step forward in our on-going efforts.

It is a collaborative partnership that combines the unique strengths and resources of a renowned training and capacity building institution, the UCSF Pacific AIDS Education and Training Center (PAETC), and an internationally recognized leader in HIV prevention research, the UCSF Center for AIDS Prevention Studies (CAPS).

Through PAETC we provide training and educational activities related to the clinical management of HIV. With this new grant, we can assist in ensuring that clinical providers provide appropriate care for transpeople in a welcoming environment, said CoE principal investigator, Michael Reyes, MD, MPH, from UCSF PAETC.

The CoE provides a vital role in disseminating essential information and best practices among caregivers and community based organizations across the state. The CoE's Community Advisory Board is drawn from community members throughout California and works to vigorously sustain the critical dialogue that needs to take place between a community facing a public health crisis and providers tasked with responding to that crisis, according to Reyes.

The Center provides consultation and technical assistance to community-based organizations that provide HIV prevention services to transpeople and we wish to improve or expand those services. We help agencies stay informed of research findings as they implement their programs and we learn from providers and the community about directions that future research should take to improve HIV prevention outcomes among transpeople, said Jae Sevelius, PhD, CoE co-principal investigator from the UCSF CAPS.

UCSF's Lesbian, Gay, Bisexual, Transgender Resource Center helped develop the proposal for the CoE.

Clinical trial finds microbicide promising as HIV prevention method for women

Thu, 05 Mar 2009 05:00:00 PST

( from http://www.rxpgnews.com ) March 5, 2009 -- A clinical trial involving more than 3,000 women in the U.S. and southern Africa demonstrates for the first time the promise of a vaginal microbicide gel for preventing HIV infection in women. According to findings presented at the Conference on Retroviruses and Opportunistic Infections (CROI), one 0.5 % dose of a microbicide designed to prevent HIV from attaching to cells in the genital tract, was 30% effective. While the results are encouraging, researchers on the study, known as HPTN 035, report that additional evidence is needed to determine more definitively its effectiveness.

These findings provide the first signal that a microbicide gel may be able to prevent women from HIV infection, says Salim S. Abdool Karim, MD, PhD, professor of clinical Epidemiology at Columbia University Mailman School of Public Health, pro vice-chancellor (research) at the University of KwaZulu-Natal in Durban, South Africa, and director the Center for the AIDS Program of Research in South Africa, who led the multi-center study for the U.S.-based Microbicide Trials Network (MTN). Indeed, for the millions of women at risk for HIV, especially young women in Africa, there is now a glimmer of hope. But these findings also indicate that more research is needed; we can't yet say that we have an effective microbicide.

Microbicides are substances intended to reduce or prevent the sexual transmission of HIV and other sexually transmitted infections when applied topically. Several candidate microbicides are being tested in clinical trials, although none is yet approved or available for use. Earlier trials have yielded disappointing results or were stopped prematurely.

Currently, women comprise half of all people worldwide living with HIV. In sub-Saharan Africa, women represent nearly 60 % of adults living with HIV, and in several southern African countries young women are at least three times more likely to be HIV-positive than young men. In most cases, women become infected with HIV through sexual intercourse with an infected male partner. Although correct and consistent use of male condoms has been shown to prevent HIV infection, women often cannot negotiate condom use with their male partners. An effective microbicide could provide women with an HIV prevention method they initiate.

HPTN 035 evaluated the safety and effectiveness of two candidate microbicides for preventing male-to-female sexual transmission of HIV. The study was conducted between February 2005 and September 2008 and involved 3,099 women at six sites in Africa and one in the United States. In Africa, the sites were located in Durban and Hlabisa, KwaZulu-Natal, South Africa; Harare, Zimbabwe; Lusaka, Zambia; Blantyre, Malawi; and Lilongwe, Malawi. The U.S. site was in Philadelphia.

I am particularly impressed by and grateful to the women who took part in HPTN 035, commented Sharon Hillier, PhD, vice chairman and professor, department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, and MTN principal investigator. We have reached an important milestone in HIV prevention research, and these women deserve credit for the success of the study.

High rate of HIV treatment interruption among newly released prison inmates

Wed, 25 Feb 2009 00:38:29 PST

( from http://www.rxpgnews.com ) Approximately 80 percent of HIV-infected Texas prison inmates did not fill an initial prescription for antiretroviral therapy within 30 days of their release from prison, potentially increasing their risk for harmful health consequences because of an interruption of treatment, according to a study in the February 25 issue of JAMA.

"The U.S. prison system has become an important front in the effort to treat and control the spread of human immunodeficiency virus (HIV) infection, serving as the principal screening and treatment venue for thousands of individuals with or at high risk for HIV infection who have limited access to community-based health care. Many inmates are offered HIV testing for the first time while incarcerated, and three-quarters of inmates with HIV infection initiate treatment during incarceration," the authors write.

Because the majority of former inmates are without private or public health insurance for the first several months after release, accessing antiretroviral therapy (ART) in a timely manner represents a challenge. "Those who discontinue ART at this time are at increased risk of developing a higher viral burden, resulting in greater infectiousness and higher levels of drug resistance, potentially creating reservoirs of drug-resistant HIV in the general community," they add. The extent to which HIV-infected inmates experience ART interruption following release from prison is unknown.

Jacques Baillargeon, Ph.D., of the University of Texas Medical Branch, Galveston, and colleagues conducted a study in the nation's largest state prison system to determine the proportion of HIV-infected inmates who filled a prescription for ART medication within 60 days following their release from prison. The study included all 2,115 HIV-infected inmates released from the Texas Department of Criminal Justice prison system between January 2004 and December 2007 who were receiving ART before release.

Among the entire study group, an initial prescription for ART medication was filled by 115 (5.4 percent) of the former inmates within 10 days of release, by 375 (17.7 percent) within 30 days, and by 634 (30.0 percent) within 60 days. The authors found that Hispanic and African American inmates were less likely to fill a prescription within 10 days and 30 days compared with non-Hispanic whites. Inmates with an undetectable viral load were more likely to fill a prescription than inmates with a detectable viral load at release. Inmates released on parole were more likely to fill a prescription within 30 days and 60 days than inmates with a standard, unsupervised release. Inmates who received formal assistance in completing an AIDS Drug Assistance Program application were more likely to fill a prescription than inmates who received no such assistance.

"In this 4-year study of HIV-infected inmates released from the nation's largest state prison system, we found that only 5 percent of released inmates filled a prescription for ART medications soon enough (i.e., within 10 days after release) to avoid treatment interruption," the authors write. In all of the subgroups examined, at least 90 percent of the former inmates experienced a treatment interruption; more than 70 percent had a treatment interruption that lasted at least 30 days, and more than 60 percent had a treatment interruption that lasted at least 60 days.

"These exceedingly high rates of treatment interruption suggest that most inmates face significant administrative, socioeconomic, or personal barriers to accessing ART when they return to their communities. Future prospective and in-depth qualitative studies are needed to more rigorously examine these barriers. Adequately addressing a public health crisis of this scale and complexity will require carefully coordinated efforts between academic institutions, the criminal justice system, and public health agencies," the researchers write. "In particular, greater coordination between state and local agencies, health care institutions, and community-based organizations is needed to reduce this high rate of treatment interruption among newly released inmates."

Case Western Reserve University faculty named 2009 NorTech Innovation Award winner

Mon, 23 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) NorTech, in partnership with Crain's Cleveland Business, today presented a 2009 NorTech Innovation Award to Eric J. Arts, Ph.D., for his development of a Biotech Platform to Detect, Monitor, and Treat Viral Diseases. Dr. Arts and his research team developed a set of diagnostic tests used by physicians and researchers to monitor the success of anti-HIV treatment by determining drug resistance and disease strength of the virus. The technology can also be used in academic research to better understand HIV/AIDS and to develop vaccines. Dr. Arts is an Associate Professor of Medicine in the Division of Infectious Diseases, Department of Medicine at Case Western Reserve University School of Medicine. He is also Director of the Uganda Laboratory Core for the Case Western Reserve University Center for Aids Research.

It is an honor to receive the prestigious NorTech Innovation Award, said Dr. Arts. My team and I appreciate this recognition of our decades of work and commitment to advancing the treatment and quality of life for patients with HIV/AIDS.

Dr. Arts is highly respected by his peers in the field of infectious disease. His research found that the heterogeneity of HIV type 1 has a significant impact on viral fitness, disease progression in the patient, emergence of drug resistance, and development of an effective vaccine. Although encompassing a broad range of topics, all of his research projects are related to HIV type 1 genetic diversity.

Dr. Arts and his laboratory are a source of great pride for the School of Medicine. Their work is an excellent example of our institution's focus on translational research which ultimately results in improved care for patients, said Pamela B. Davis, M.D., Ph.D., Dean, School of Medicine, Case Western Reserve University. We look forward to this technology's next generation of testing for conditions, such as hepatitis C, and the development of real-time influenza vaccines based on a season's dominant virus strains.

Since 2000, NorTech has been recognizing technology leaders working at the forefront of research, development, and technology commercialization in Northeast Ohio, said Dorothy C. Baunach, President and CEO, of NorTech. We believe the innovations being recognized today will lay the groundwork for building new technology industries for the future of our region.

Earlier this month, Case Western Reserve University and Diagnostic HYBRIDS Inc. signed an exclusive worldwide licensing agreement granting Diagnostic HYBRIDS rights to a novel yeast-based virus cloning technology invented by Dr. Arts. His technology is a step towards personalizing medicine based on the needs of each patient. In this case, physicians can use this assay to determine the effectiveness of a patient's anti-HIV medication. Compared with existing drug-resistance technology, Dr. Arts' technology is more sensitive, inexpensive, and provides better analysis of the body's response to medication.

UCSF symposium considers biomedical approaches to HIV/AIDS prevention

Thu, 12 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) New and emerging biomedical approaches to HIV/AIDS prevention will be the focus of a daylong symposium on February 24 sponsored by the UCSF-Gladstone Institute for Virology and Immunology Center for AIDS Research (CFAR) and the UCSF Center for AIDS Prevention Studies.

Defining new biomedical approaches capable of curbing the global HIV epidemic is a high priority. This symposium will provide a timely overview of the most promising advances, said Warner C. Greene, MD, PhD, director of the Gladstone Institute for Virology and Immunology (GIVI) and co-director of the UCSF-GIVI CFAR.

Use of antiretrovirals for HIV prevention in uninfected individuals at high risk for infection, herpes suppression, male circumcision and the successful treatment of HIV-infected individuals with antiretrovirals are some of the approaches that will be under discussion at the symposium.

With the setbacks in HIV vaccine development and a still expanding epidemic, we are forced to consider all options to prevent HIV transmission. Along with ongoing and critical efforts to understand and reduce behaviors of risk, we are deeply interested in how biologic barriers may be employed in effective prevention, said Paul A. Volberding, MD, UCSF-GIVI CFAR co-director and professor and vice-chair, UCSF Department of Medicine.

Antiretroviral therapies are extremely potent and convenient in reducing HIV replication and might be part of a comprehensive effort to couple treatment with prevention. In selected situations, antiretroviral therapy may be used solely as prevention in persons otherwise unable to avoid potential exposure to infection. These and other topics promise to generate a lively and informative debate, added Volberding.

In addition to examining biomedical approaches, the symposium will address topics related to the conduct of clinical trials investigating these approaches and issues associated with implementation and scale-up of biomedical prevention interventions once they have been proven effective in clinical trials.

Understanding the impact of behavioral issues such as consistent pill-taking or proper product usage as well as the difficulties of measuring these through trial participants' self reporting is crucial to successfully conducting clinical trials of biomedical approaches, said Stephen F. Morin, professor of medicine and director of the UCSF Center for AIDS Prevention Studies (CAPS).

Moreover, the symposium will address the social science components involved in the implementation and scale-up of interventions following positive results in a clinical trial. For instance, male circumcision trials have shown success in preventing HIV acquisition but, as we will discuss, there are significant cultural, social and behavioral considerations that must be addressed if the intervention is going to be successfully implemented, said Morin.

The symposium will be held at UCSF's Mission Bay campus at the Mission Bay Conference Center beginning at 9 a.m. The full program can be found, along with information about parking, mass transit and registration online at

Model of pre-exposure prophylaxis against HIV forecasts benefits, potential cost-effectiveness

Mon, 09 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) WHAT: For every two people who begin treatment for HIV infection globally, five others become newly infected. Therefore, preventing new HIV infections is the foremost strategy for ending the HIV/AIDS epidemic. One potential prevention strategy involves giving antiretroviral drug regimens to people who are at high risk for HIV to protect them from infection. Important questions about this experimental approach, known as pre-exposure prophylaxis (PrEP), remain unanswered, including, Could PrEP cut the lifetime risk of HIV infection? Would PrEP be cost-effective?

A new mathematical model of PrEP use in U.S. populations at high risk for HIV infection takes these and other questions into account and predicts the prevention strategy could substantially reduce the lifetime risk of HIV infection. According to the model, the cost-effectiveness of PrEP could vary substantially depending on the age of the target population, their risk behaviors, the annual rate of new HIV infections in the target population, and the efficacy and cost of antiretroviral PrEP drugs. These findings are reported by a team of scientists led by A. David Paltiel, Ph.D., of Yale University, and supported by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Mental Health and the National Institute on Drug Abuse, all part of the National Institutes of Health.

Dr. Paltiel says his team's model is the first to establish performance benchmarks that clarify the clinical, epidemiologic and economic circumstances under which PrEP would represent good patient care, good public health and good value.

To create their model, the researchers made several conservative assumptions: 1) PrEP is 50 percent effective; 2) the target population is American men who have sex with men who average 34 years of age; 3) 1.6 percent of this population becomes newly infected with HIV annually; and 4) the antiretroviral drugs (tenofovir and emtricitabine) cost $9,000 per year. With these parameters, the model predicts PrEP would cut the lifetime risk of HIV infection from 44 percent to 25 percent. However, the life expectancy of the target population from the time after beginning PrEP would increase by less than a year (from 39.9 years to 40.7 years) and PrEP would not be cost-effective by current U.S. standards. Yet with modest improvements in the efficacy of antiretrovirals used preventively, more realistic estimates of their cost (potentially as low as $900 per year), or a target population that is younger and at higher risk, the model predicts PrEP might be as cost-effective as other widely recommended public health and medical interventions in the United States. With large improvements in these parameters, the potential benefits of PrEP could be substantial, according to the model. For example, assuming PrEP will be 90 percent effective leads the predicted lifetime risk of HIV infection to fall from 44 percent to 6 percent.

Breast fed babies on Nevirapine prophylaxis are at risk of developing drug-resistant HIV

Mon, 05 Jan 2009 11:50:50 PST

( from http://www.rxpgnews.com ) Babies born to HIV-positive mothers and given the antiretroviral drug nevirapine through the first six weeks of life to prevent infection via breast-feeding are at high risk for developing drug-resistant HIV if they get infected anyway, a team of researchers report. But the investigators highlight the proven superiority of the six-week regimen in preventing mother-to-child HIV transmission in breast-fed infants.

In a study led by researchers at Johns Hopkins Children's Center, risks of drug resistance in the first year of life were compared in Indian infants getting a standard single dose of nevirapine at birth and those on the six-week regimen.

"While extended nevirpaine prophylaxis dramatically reduces HIV transmission during the first six weeks of life, our data show that if infection does occur, it will most likely be with strains resistant to nevirapine, making HIV much harder to treat early with nevirapine," says senior investigator Deborah Persaud, M.D., a pediatric HIV expert at Hopkins Children's. "But until other interventions become available, the extended nevirapine regimen remains a reasonable way to prevent infections through breast-feeding."

Published in the Jan.1 issue of Public Library of Science One (PLoSOne), the research report emphasized that in the developing world especially, where bottle feeding is not safe, too expensive or simply unavailable, the extended nevirapine therapy remains one of the best ways to reduce mother-to-child transmission of HIV through breast milk.

Given the high risk of death from HIV in infancy, the benefits of fewer infections still outweigh the risk of increased resistance, the researchers conclude.

The findings also suggest that because of their higher risk for acquiring resistant HIV strains, infants given extended courses of nevirapine—should they get infected—should receive treatment with protease inhibitors (PIs), which are effective against nevirapine-resistant strains.

"In the developing world testing for resistance is not available or too expensive," Persaud says, "so if extended nevirapine regimens become widespread, PIs should be made available as a first line of treatment early on for all infants who get infected despite prophylaxis."

The new report comes on the heels of two separate multi-center studies from Johns Hopkins and other institutions, published in 2008, showing that a six-week regimen with nevirapine or a 14-week regimen with nevirapine slashed the risk of HIV infection from breast-feeding by 46 percent and 66 percent, respectively.

For the current study, investigators analyzed samples from 74 Indian babies infected with HIV before, during or after birth. Of the 74 infants, 22 were infected before birth, 19 were infected during birth or during early breastfeeding (three to six weeks after birth) and 33 were infected during late breast-feeding (around six months after birth). Of the 19 infants infected through breastfeeding in the first six weeks of life, four were given daily nevirapine for six weeks, and 15 received a single dose at birth. All four babies on extended nevirapine developed resistant strains of the virus, while only four of the 15 given a single dose tested positive for resistant strains after infection.

It is important to keep in mind that while the risk of resistance is higher with extended nevirapine regimens once infection occurs, the risk of acquiring HIV with extended regimens is dramatically reduced, the investigators say. Thus, in the long run, extended nevirapine regimens do not lead to more resistant cases than the single-dose regimens because single-dose regimens also carry some risk of resistance and are also less effective in preventing new infections.

Indeed, when researchers compared resistance among infants infected during late breast-feeding, the gap in resistance risk virtually disappeared. Fifteen percent of the 13 infants given extended nevirapine developed resistance, and so did 15 percent of the 20 infants who received a single dose of the drug.

When investigators used more sensitive assays to detect nevirapine-resistant mutations that are normally not detected by standard tests, the proportion of infants with resistant strains who had received single-dose nevirapine went up from 38 percent to 59 percent among the 29 infants who got the single dose, but remained unchanged in the group receiving the six-week regimen, 92 percent of 12. Likewise, the proportion of infants testing positive for resistance went up in the group infected after six weeks of age. In that group, 31 percent of 13 infants on the extended regimen tested positive for resistant strains, and 40 percent of 20 infants who got the single dose had resistant strains. However, researchers say, the clinical significance of mutations that are not detected by standard testing remains unclear.

The infants in this trial were infected with HIV subtype C, but previous studies have shown that the six-week regimen increases resistance in infants who get infected with other HIV subtypes as well.

Despite the risk of HIV transmission, breast-feeding for at least six months is widely encouraged by the World Health Organization (WHO) and other organizations as a proven factor in better infant survival. In 2007 alone, 420,000 infants acquired HIV in utero, during birth or during breast-feeding, according to WHO estimates. HIV infection is estimated to occur in 1 out of 10 breast-fed infants, with many of the infections occurring in the first six to 14 weeks of life.

New book covers full spectrum of neuro-AIDS disorders

Tue, 09 Dec 2008 05:00:00 PST

( from http://www.rxpgnews.com ) In the decade-plus since the introduction of highly active antiretroviral therapy (HAART) for HIV infection, doctors have come to understand that the brain can serve as a reservoir for resistant virus, where it causes a whole different set of symptoms scientists call neuro-AIDS. A new book from ASM Press, The Spectrum of Neuro-AIDS Disorders: Pathophysiology, Diagnosis, and Treatment, presents the full scope of research on the neurological and neurobehavioral implications of HIV/AIDS in a single, unique volume.

This book represents a compendium of knowledge that is unique to the field of neuro-AIDS. At this point in the era of highly active antiretroviral therapy (HAART), we have come to appreciate, more than ever before, the implications of the brain as an organ that becomes a reservoir for resistant HIV, contributing to a deleterious impact of this chronic infection on patient functioning. The book is designed to present a coordinated focus on the integration of knowledge regarding the pathophysiological bases, diagnostic approaches, and clinical treatment strategies specific for neuro-AIDS conditions in the HAART era today, says Karl Goodkin of Cedars-Sinai Medical Center and the University of California-Los Angeles who co-edited the book with Paul Shapshak of the University of South Florida College of Medicine and Ashok Verma of the University of Miami Miller School of Medicine.

In this book, noted researchers from all over the world examine the wide range of HIV-associated neurological and neurobehavioral disorders. Neuro-AIDS can affect the entire neuraxis, resulting in physiological, neurological, and neurobehavioral deficits ranging from distal sensory polyneuropathy and primary CNS lymphoma to HIV-associated neurocognitive impairment and disorders including HIV-associated dementia. Toxicities of the antiretroviral medications themselves are a serious concern.

This book presents the wide variety of HIV-associated disorders and comorbidities with a look at the pre-HAART literature as well as the latest findings from the post-HAART era. Pathophysiology and selected neuroimaging techniques for diagnosis and assessment are examined in detail. In addition, this volume stands out for its chapters on specific patient populations such as women, children, minorities, and older persons, as well as special chapters addressing medico-legal and end-of-life concerns. The book concludes with a look at global issues and the future of neuro-AIDS in the HAART era.

While the literature in this area advances rapidly, we hope that this volume will retain its appeal over time by its structured approach to the epistemology of neuro-AIDS knowledge. We anticipate that this presentation of the conceptual underpinnings of the neuro-AIDS field will allow new data to continue to be added to the organizational tree of knowledge, resulting in a timeless value for its readers, says Goodkin.

Individuals with HIV have higher risk of non-AIDS cancers

Tue, 18 Nov 2008 05:00:00 PST

( from http://www.rxpgnews.com ) WASHINGTON, D.C. - The risk of non-AIDS cancer is higher for individuals infected with HIV than for the general population, according to a meta-analysis presented here at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.

Compared with the general population, the risk for non-AIDS cancers was 2.3 times higher for men with HIV and 1.5 times greater for women with HIV. Among individuals with HIV, however, incidence rates were similar for those with AIDS and those without, relative to the general population.

Although the researchers did not examine why non-AIDS cancers may occur at a greater rate among individuals with HIV, clinicians should be aware of this potential increased risk when examining patients with HIV, said Meredith Shiels, M.H.S., an epidemiologist at Johns Hopkins School of Public Health.

In particular, clinicians of HIV-infected patients should inquire about well-known modifiable cancer risk factors, she said. For example, the prevalence of cigarette smoking, which is a cause of many types of cancer, is known to be higher among HIV-infected individuals.

Modern drug therapy has led to a longer life for patients with HIV. Because cancer risk increases with age, investigating the risk of cancer among patients with HIV is important. Although some cancers are known to be associated with HIV, such as Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical cancer, limited research has been conducted on risk of non-AIDS cancers.

Shiels and her colleagues analyzed data from 11 U.S. and international studies comparing cancer incidence in individuals with HIV with the general population. Individual studies were excluded if they included data that overlapped with more recent studies. The meta-analysis combined standardized incidence ratios from each study and examined whether they differed by gender and prior AIDS diagnosis.

We observed an overall elevated risk for all non-AIDS cancers combined among HIV-infected individuals compared with the general population, Shiels said. The elevated risk appears to be greater among men than women.

Relative to the general population, the incidence of non-AIDS cancer appeared higher for individuals with and without an AIDS diagnosis. When the researchers adjusted the data for gender and study design, the estimates were similar: the risk of non-AIDS cancer was about two times greater than the general population for HIV-infected individuals both with and without AIDS.

When managing patients with HIV, clinicians should be aware of the potential for increased risk of non-AIDS related cancers. It is important for regular cancer screening to take place and for clinicians to encourage patients to modify factors that could affect cancer risk, such as cigarette use and nutrition.

The meta-analysis did not investigate possible reasons for the increased risk of non-AIDS cancers among patients with HIV. Understanding the link may lead to better management of cancer among patients with HIV and could be a topic for future study.

Key protein found that helps HIV assault brain

Sun, 16 Nov 2008 15:26:27 PST

( from http://www.rxpgnews.com ) Washington, Nov 15 - Researchers have isolated a key protein that explains why antiviral drugs can fend off the HIV in the body, but not in the brain.

The new study traces how key steps taken by Tat, a protein that helps HIV operate, replicate and infect cells, enables HIV to attack the brain, bringing about severe inflammation.

Researchers identified the receptor that Tat uses to attack neurons, whose effects they reversed by blocking the receptor.

'Suddenly the brain environment turns from nurturing to toxic. Cells are on overdrive, spending a lot more energy to do the same things they used to do easily,' said Harris Gelbard, neurologist at Rochester University Medical Centre.

'The current medications give many patients a new lease on life. But the virus is still taking a toll on the brain, even when the virus appears to be much less active elsewhere in the body,' said Gelbard, the paper's co-author.

The discovery of a major molecular player in the process opens up new ways of exploring how to prevent or treat HIV's neurological effects, for which there is no currently approved treatment, said a Rochester release.

Much of the molecular action that underlies HIV's attack on the brain also occurs in other diseases, such as Parkinson's and Alzheimer's diseases, and the results spell progress for those conditions as well.

The powerful antiviral drugs that keep many HIV patients healthy for years don't completely eradicate the virus from the body, and in the brain, even the very low levels of that remain cause relentless damage.

Scientists have observed that a large percentage of HIV patients - perhaps up to half - show evidence of neurologic disease from the virus.

These findings were published online in the Nov 13 issue of PloS One.

Familes fear HIV transmission if parent is infected

Tue, 11 Nov 2008 14:47:46 PST

( from http://www.rxpgnews.com ) Washington, Nov 6 - Two-thirds of families with an HIV-infected parent experienced fears about the virus spreading at home, according to a joint study.

The qualitative study is the first to interview multiple family members, including minor children, in families with an HIV-infected parent.

'We found that many of the worries were based on misconceptions about how HIV is spread,' said study co-author Burt Cowgill, staff researcher at the University of California Los Angeles -/RAND Centre for Adolescent Health Promotion.

'We also learned that HIV-infected parents had legitimate concerns about contracting infections such as a cold, flu or chicken pox while caring for a sick child,' added Cowgill.

'This knowledge could help paediatricians to address children's specific fears about HIV transmission as well as help clinicians who care for the HIV-infected parents.'

Between March 2004 and March 2005, the team conducted interviews with 33 HIV-infected parents, 27 of their children aged nine to 17, nineteen adult children and 15 caregivers -.

All HIV-infected parents had previously participated in RAND's HIV Cost and Services Utilisation Study, a national probability sample of people over 18 with known HIV infection, according to a UCLA release.

Interview questions were open-ended and broad to elicit a detailed description of family members' experiences. In addition, follow-up questions focused on whether respondents' fears subsided over time and what was done in the household to address them.

In a majority of the families, participants reported HIV transmission-related fears in the household. Concerns included acquiring HIV through contact with blood from a parent's cut, through saliva by sharing a bathroom or kissing, or by sharing food or beverages.

HIV-infected parents were also concerned about catching an opportunistic infection from a sick child or other family member, and they were especially concerned about caring for a child with chicken pox, a cold or the flu.

'Fears about disease may substantially affect the relationship between the HIV-infected parent and child,' said co-author Mark Schuster, chief of general paediatrics at Children's Hospital Boston and professor of paediatrics at Harvard Medical School.

'It is critical not only to provide children with age-appropriate information on how the disease is transmitted, but also to clear up any misconceptions.'

The findings are scheduled for publication in a forthcoming issue of Paediatrics.

Herpes drug inhibits HIV replication

Tue, 11 Nov 2008 13:55:42 PST

( from http://www.rxpgnews.com ) Washington, Nov 7 - Anti-herpes drug acyclovir can slow down HIV infection by targeting an enzyme, but is also instrumental in the emergence of multi-drug resistant HIV variants.

HIV and herpes - are two of the most common sexually transmitted diseases worldwide, and individuals frequently become infected with both.

In such cases, the two viruses interact with each other; the presence of HIV often results in more frequent HSV lesion outbreaks, while HSV can speed up the progression of HIV to AIDS.

Considering their interaction, recent studies showing that acyclovir treatment could reduce HIV viral load in co-infected patients were not surprising, and attributed to an indirect effect of HSV suppression.

However, Moira McMahon and colleagues at Johns Hopkins decided to look whether the effects on HIV might be direct.

They used a sensitive infection assay of white blood cells and found that acyclovir can directly inhibit HIV replication, the medical school said in a statement. The drug specifically targeted RT, the key HIV enzyme that converts the virus' RNA into DNA so it can be replicated.

However, acyclovir treatment had some unexpected results; five days after initial infection, a mutant version of HIV - appeared in the cells, and within 94 days spread to comprise over 90 percent of the viral population.

The V75I strain is part of the resistance pathway to many drugs, including the commonly used RT inhibitors. What this means, the authors note, is that acyclovir could be a great model for designing future HIV treatments, but also could be a risky drug if given to HSV patients co-infected with HIV by potentially promoting cross-resistance to current treatments.

These findings appeared in Journal of Biological Chemistry online Friday.

New hope for HIV treatment: Cells exhausted from fighting HIV infection can be revitalized

Mon, 10 Nov 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Toronto and the University of California, San Francisco, have revealed new hope for HIV treatment with the discovery of a way to 'rescue' immune cells that are exhausted from fighting off HIV infection.

The team lead by Drs. Mario Ostrowski, of the University of Toronto's Faculty of Medicine, and Douglas Nixon, of the Division of Experimental Medicine at the University of California, San Francisco, has discovered that a molecule called Tim-3 is present at high levels on poorly functional immune system cells which are 'exhausted' from fighting HIV infection. The researchers found that blocking the activity of Tim-3 on these cells improved their function and allowed them to rejoin the battle against HIV.

In the typical course of HIV infection, an initial burst of very high levels of the HIV virus is brought partially under control by the infected person's immune system, specifically by an immune system cell called a CD8+ killer T cell. In the majority of cases without antiretroviral drug treatment, the immune system is eventually overwhelmed and progression to AIDS occurs, said co-principal author Brad Jones, a PhD candidate in Immunology at the University of Toronto.

Progression to AIDS is associated with a breakdown in those CD8+ T immune system cells. In a typical viral infection, those cells rapidly multiply, kill off virus-infected cells and stimulate other cells in the immune system. But over time, in the battle to fight off HIV infection these CD8+T cells become less functional and enter into a state known as 'exhaustion.' The mechanisms that lead to this exhausted state are not well known, said Jones. We felt that if we could understand these mechanisms then we may be able to intervene and re-energize the immune system. The research team theorized that this exhausted state may result from the Tim-3 molecule sending a signal to shut down CD8+ T cells in HIV-infected individuals.

The researchers observed that Tim-3 expression on T cells, in particular the CD8+ T cells, associated remarkably strongly with clinical parameters of HIV disease progression in a diverse group of HIV-infected individuals. From these results we predicted that the Tim-3 pathway might be manipulated to potentially confer clinical benefit and serve as a promising new target for clinical intervention to decrease the severity of HIV infection, said co-principal author Lishomwa Ndhlovu, MD, PhD in the Division of Experimental Medicine, University of California, San Francisco.

To test this, we produced a molecule capable of blocking the Tim-3 signal and studied the effect that this had on CD8+ T cell function in vitro, said Mario Ostrowski, MD, Associate Professor in the Department of Immunology, University of Toronto. We observed that blocking the Tim-3 pathway rescued those cells and restored their ability to fight off infection.

This discovery, published in the November 24th issue of the

Panel advocates improved understanding of hepatitis B and screening of high-risk populations

Thu, 23 Oct 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Management of hepatitis B is a challenge for physicians and patients due to an incomplete understanding of the disease course, complex treatment indications, and the lack of large studies focusing on important health outcomes. To examine these issues, the NIH convened an independent, impartial panel this week to weigh the available evidence on the management of hepatitis B.

While more than 95 percent of U.S. children are routinely vaccinated for hepatitis B, the vaccine does not protect individuals already infected with the virus. In unprotected individuals, acute infection with the hepatitis B virus is usually resolved by the body's immune system and does not cause long-term problems. The transition from acute to chronic infection appears to occur when the immune system does not effectively destroy and clear virus-infected cells.

A number of antiviral therapies approved by the U.S. Food and Drug Administration are available for use in fighting chronic hepatitis B infection including interferons and nucleos(t)ides. We know that these therapies have positive effects on indicators such as viral load, but further controlled trials are needed to substantiate that these agents prevent disease progression to liver failure, cancer, or death, explained panel chair Dr. Michael F. Sorrell, Professor of Medicine at the University of Nebraska Medical Center.

To address this gap in the evidence, the panel recommended several avenues for future research. Among these, they gave top priority to large andomized studies, including placebo-controlled trials, testing single drug and combination therapies' effects on liver failure, cancer, and death. The panel also proposed representative prospective cohort studies to define the natural history of the disease to optimize management across diverse patient subgroups. This would also help decide which patients are most in need of immediate therapy and which could be carefully followed without drug therapy.

The panel is encouraged by the National Institute of Diabetes and Digestive and Kidney Disorders' plans to launch the Hepatitis B Clinical Research Network to promote translational research on this challenging condition. It is anticipated that the recommendations in the consensus statement will inform the consortium's research agenda.

The panel identified elevated hepatitis B DNA blood levels and elevated levels of ALT (alanine aminotransferase, a liver enzyme) as the most important indicators for progression to cirrhosis and liver cancer (hepatocellular carcinoma). Older age, male sex, family history of liver cancer, coinfection with hepatitis C or HIV, and elevated blood levels of hepatitis B DNA were also found to be key predictors.

The panel recommends routine hepatitis B screening for newly arrived immigrants from countries where hepatitis B prevalence is greater than two percent. These practices are intended to facilitate access to care for infected individuals and their families and to provide valuable data on disease prevalence, not to exclude immigrants in any way.

The panel recommends therapy for certain patients, including those with acute liver failure and complications from cirrhosis. However, immediate therapy is not indicated for patients with inactive forms of the disease.

The panel's complete consensus statement will be available later today at

Integrating antiretroviral therapy with TB treatment for co-infections reduces mortality

Thu, 16 Oct 2008 04:00:00 PST

( from http://www.rxpgnews.com ) October 16, 2008 -- A South African treatment study conducted by researchers in the Department of Epidemiology at the Mailman School of Public Health shows that mortality among TB-HIV co-infected patients can be reduced by a remarkable 55%, if antiretroviral therapy (ART) is provided with TB treatment at the same time. The randomized, known as the SAPIT (Starting Antiretrovirals at three Points in Tuberculosis) trial, randomly assigned TB-HIV co-infected patients to receive ART. Patients who received ART together with their TB treatment (integrated treatment arm) were compared with patients assigned to receive ART upon completion of TB treatment (sequential treatment arm).

The study shows that integrating TB and HIV treatment and care saves lives, says Salim S. Abdool Karim, MD, PhD, professor of clinical Epidemiology at the Mailman School of Public Health and director of the Centre for the AIDS Program of Research in South Africa (CAPRISA), who led the SAPIT trial. The trial was conducted at the CAPRISA eThekwini TB-HIV Clinic which is attached to the largest TB clinic in Durban, South Africa. The study was initiated in June 2005 and completed enrollment of 645 patients with TB and HIV co-infection in July 2008. It is estimated that about 70% of all TB patients in South Africa are infected with HIV, or about 250,000 of the 353,879 TB patients diagnosed in 2007.

As a result of the higher mortality rate in patients in the sequential treatment arm versus the mortality rate for those patients in the integrated treatment arm, the study's independent Safety Monitoring Committee recommended in their review of the trial in September 2008 that the sequential arm of the trial be stopped and that ART be initiated in this group as soon as possible. The Committee further recommended that the two sub-groups within the integrated treatment arm (early TB-HIV treatment and post-intensive phase TB-HIV treatment) should continue as per protocol.

Dr. Peter Piot, executive director of UNAIDS, commented: These important results show that a ''two diseases, one patient, one response integrated approach to TB/HIV treatment avoids unnecessary deaths from TB, the leading cause of death in people living with HIV in Africa. TB is the most common disease occurring in the late stages of HIV infection in southern Africa. As a result, many people throughout southern Africa are first identified as HIV infected when they develop TB. The findings of the SAPIT study call for the accelerated implementation of routine HIV testing in TB treatment services.

The SAPIT trial results provide compelling evidence to support the World Health Organization's call for the greater collaboration between TB and HIV treatment services and provide empiric evidence of the benefits from the initiation of antiretroviral therapy in TB-HIV co-infected patients. Dr Paul Nunn, of the Stop TB Department at the World Health Organization commented, The results to date clearly show the urgent necessity to make ART available to HIV infected patients with TB worldwide. In South Africa alone, it would result in an additional 100,000 to 150,000 TB patients being initiated on ART resulting in about 10,000 deaths being averted each year.

Ambassador Mark Dybul, Coordinator of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) said: Scaling up collaborative TB/HIV activities is a priority for PEPFAR. We remain committed to increasing screening for both HIV and TB, which will allow greater numbers of patients to benefit from these study results.

HIV drug maraviroc effective for drug-resistant patients

Wed, 01 Oct 2008 04:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Oct. 2, 2008) -- As many as one quarter of HIV patients have drug resistance, limiting their treatment options and raising their risk for AIDS and death. Now, maraviroc, the first of a new class of HIV drugs called CCR5 receptor antagonists, has been shown to be effective over 48 weeks for drug-resistant patients with R5 HIV-1, a variation of the virus found in more than half of HIV-infected patients.

Results of the two Phase 3 multicenter MOTIVATE (Maraviroc Plus Optimized Therapy in Viremic Antiretroviral Treatment Experienced Patients) studies led by NewYork-Presbyterian Hospital/Weill Cornell Medical Center's Dr. Roy Gulick and published in the October 2 issue of the New England Journal of Medicine (NEJM) find that the drug, taken with an optimized standard HIV drug regimen, resulted in significantly greater suppression of the virus at 48 weeks, with concurrent increases in immune system T-cell counts, when compared with placebo. Rates of side effects were not different between the maraviroc and placebo groups.

Preliminary results of these studies led to FDA approval of maraviroc in August 2007.

Because it is from a new class of HIV medications known as HIV entry inhibitors, people living with HIV generally will not have resistance to maraviroc because they have not been exposed to any drugs from the class previously. Unlike earlier HIV drugs that target the virus, maraviroc acts on the human T-cell, binding to it in such a way that prevents HIV from binding and subsequently infecting the T-cell.

It is now possible to expect that a majority of treatment-experienced patients who experience failure on their current HIV drugs will regain control of their HIV infection with maraviroc combined with other newer antiretroviral drugs. This is an important step forward, says study principal investigator Dr. Roy Gulick, who is professor of medicine and director of the Cornell HIV Clinical Trials Unit of the Division of International Medicine and Infectious Diseases at Weill Cornell Medical College, and a practicing physician at NewYork-Presbyterian Hospital in New York City. Suppressing virus levels and increasing immune system T-cells with HIV treatment regimens helps HIV-infected people live longer, healthier lives.

The double-blind study followed 1,049 of patients with advanced HIV and resistance to three antiretroviral drug classes. Patients were randomized to receive maraviroc once-daily, twice-daily or placebo. Safety and efficacy were assessed at 48 weeks. The MOTIVATE studies comprised two identical arms: MOTIVATE1 was conducted in Canada and the U.S., while MOTIVATE2 was conducted in Australia, Europe and the U.S.

UNC receives record $181 million grant to evaluate health, poverty and gender programs worldwide

Mon, 08 Sep 2008 04:00:00 PST

( from http://www.rxpgnews.com ) The United States Agency for International Development (USAID) has awarded the Carolina Population Center at the University of North Carolina at Chapel Hill up to $181 million to continue its MEASURE Evaluation project.

The award is the largest ever received by UNC.

The award funds the monitoring and evaluation of family planning, maternal and child health, nutrition and HIV/AIDS programs around the world. The project also monitors and evaluates malaria, tuberculosis and avian influenza programs, and will expand to programs addressing poverty and gender equity.

Going into its third phase, MEASURE Evaluation builds on the previous two phases of the project and the earlier EVALUATION project which began in 1991. The project already has a presence in nearly 50 countries in Africa, Asia, Europe and Latin America and will expand to more. Besides the $181 million of project funding in this grant, the award includes the potential for countries to request evaluation activities valued at up to an additional $125 million over the five years.

The size of this award is unprecedented, said Barbara Entwisle, Ph.D., director of the Carolina Population Center (CPC) and Kenan Professor of Sociology in the UNC College of Arts and Sciences. Faculty at UNC, specifically those at the Carolina Population Center who are part of the MEASURE Evaluation team, have achieved an international reputation for excellence in evaluation research.

The funding of this latest stage of the project acknowledges the great success of the MEASURE Evaluation team in its earlier phases.

Sian Curtis, Ph.D., research associate professor of maternal and child health in the School of Public Health and a CPC fellow, is principal investigator and project director. Gustavo Angeles, Ph.D., assistant professor of maternal and child health in the School of Public Health and CPC fellow, is co-principal investigator and deputy director.

Good information is essential to improve the health of the world's population, Curtis said. This award provides a fabulous opportunity to strengthen our understanding of global health programs and improve the collection, analysis and use of population and health information.

The project's partners includes John Snow Inc., Macro International, Tulane University, The Futures Group International and Management Sciences for Health.

The MEASURE (Monitoring and Evaluation to Assess and Use Results) Evaluation project uses different strategies to collect and use data about health issues. For example, a tool for assessing and modifying HIV/AIDS prevention programs locally or nationally called the Priorities for Local AIDS Efforts (PLACE) method can identify geographic areas that contain key HIV transmission networks. The PLACE method was developed by Sharon Weir, Ph.D., research assistant professor of epidemiology in the School of Public Health and a CPC fellow.

The project will focus on developing the expertise of health workers and officials in host countries to collect, analyze and use data that are gathered. Building on its existing monitoring and evaluation training courses, researchers will launch a distance learning component to increase the number of people who are trained to monitor and evaluate health programs. Communities of practice will also be created so people from different countries who work on the same health issue can share information and learn from each other.

Combination HIV prevention can avert 12 million cases by 2015

Wed, 06 Aug 2008 11:02:51 PST

( from http://www.rxpgnews.com ) London, Aug 6 - Combination HIV prevention, if thoroughly implemented by governments and communities, can avert 12 million infections by 2015, according to experts. Right now, some 7,000 people are infected daily around the world.

A report authored by Peter Piot and Michael Bartos of the joint United Nations Programme on HIV/AIDS, Geneva said a quarter century of AIDS responses has created vast knowledge about HIV transmission and prevention, yet some 7,000 people are infected daily worldwide.

'If combination prevention is intensified as rapidly as possible from today, then some 12 million fewer HIV infections will occur if incidence at today's levels remains constant, and the annual number of new infections in 2015 will have reduced by two-thirds.'

Essential programmes have not had sufficient funding or coverage, and such programmes have often not been targeted to the populations that need them most.

The authors called for confident and unified leadership to overcome the political, cultural, and logistic barriers to effective HIV prevention.

This includes mustering support for proven interventions such as the frank education of young people, harm reduction policies for injecting drug use, and including sexual minorities in HIV programmes.

International institutions, national governments and community activists must work together to build demand for HIV prevention. Support must be rallied in every area possible, including workplaces, schools, communities and places of worship.

An active coalition between the movement for HIV prevention and the movement of people living with HIV/AIDS should also be created and linked with other social movements such as treatment activists, entrepreneurs, and women's and youth activists.

The authors urged scientists, research bankrollers and programme planners to broaden the HIV-prevention research agenda, in particular through a greater focus on operational research to help guide optimum programme scale-up.

The report appeared in British medical journal The Lancet.

HIV expert says 1 step down, 2 more to go in quest to cure AIDS

Wed, 06 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A Johns Hopkins expert in HIV and how the AIDS virus hides in the body says antiretroviral drugs have stopped HIV from replicating, the first of three key steps needed to rid people of the virus.

In an address to be delivered Aug. 6 at the XVII International Conference on AIDS, taking place in Mexico City, infectious disease specialist Robert Siliciano, M.D., Ph.D., says current drug-combination therapies can stop HIV in its tracks, with some combos suppressing its ability to make copies to less than one in a billion.

But, he says, progress is still needed in identifying where viral reservoirs persist and in finding ways to eliminate these HIV hiding places.

Indeed, it was Siliciano's team at Hopkins in 1995 that confirmed the existence of these reservoirs in immune system CD4 memory T-cells - those left behind, after an initial infection, to fight recurrences. The CD4s concentrate in the lymph nodes and spleen. Siliciano suggests that other as yet unverified viral pools could exist, citing previous studies at Johns Hopkins that, in 2006, identified adult stem cells and progenitor cells as potential hideaways for HIV.

According to Siliciano, a professor at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator, laboratory models that mimic HIV infection in these reservoir cells are key to finding drugs that can eliminate them.

We know now that HIV can be stopped, says Siliciano. Our next steps are to go after these reservoirs of HIV. And although much work needs to be done to find and eliminate them, infected people who have access to antiretroviral drugs and who take them as prescribed stand a good chance of leading normal lives.

Siliciano points out that if antiretroviral drugs can be made more accessible, affordable and less toxic, then infected people who take the drugs correctly will not develop AIDS.

Included in Siliciano's presentation are recent data from his team and researchers at the National Cancer Institute and the University of Pittsburgh, which shows that adding a fourth, more potent anti-HIV drug to existing antiviral combinations does not further suppress the number of HIV viral copies in the blood.

Adding more drugs to current regimens will not further reduce the amount of virus in the blood, says Siliciano. We have already reached rock bottom in using drugs to stop HIV from replicating. The trace amounts of virus that remain are coming from viral reservoirs, not active replication of the virus.

In 15 HIV-positive study participants already using highly active antiretroviral therapy, or HAART, to suppress the virus, researchers added either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. They found no greater suppression in viral blood levels than seen before the fourth drug was added.

Hundreds of thousands of the more than 1 million Americans infected with HIV are currently using HAART, a combination usually of three of 25 potent antiviral medications. And these drugs almost eliminate the amount of virus in the blood, lowering the number to fewer than 50 copies per cubic milliliter of blood.

Siliciano also describes the progress of four laboratory models for testing HIV reservoirs, including one developed at Johns Hopkins, in identifying all viral reservoirs, and in penetrating them with antiretroviral drugs.

There are more than 33 million people in the world living with HIV, including an estimated 950,000 in the United States and 23,000 in the state of Maryland.

Stanford study finds HIV drug can persist in mothers' milk, increasing risk to them and their babies

Tue, 05 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) STANFORD, Calif. - A drug commonly used in the developing world to prevent transmission of HIV from mother to child persists in the breast milk and blood of the mothers, putting them and their babies at risk for developing drug-resistant strains of the virus, according to researchers at the Stanford University School of Medicine.

The researchers found that the drug, nevirapine, stays in the blood and breast milk of the infected mothers for at least two weeks. During that time, the virus has ample opportunity to transform itself into drug-resistant strains of HIV, the human immunodeficiency virus that causes AIDS, which can be very difficult to treat.

In the short term, nevirapine is better than nothing, said David Katzenstein, MD, professor of infectious diseases and principal investigator of the study. But in the long term, I'm concerned about conferring resistance. If you're talking about resistance on a broad scale, it could jeopardize future treatment for mothers and infants.

Seble Kassaye, MD, instructor in infectious diseases and first author of the study, will present the results Aug. 5 at the International AIDS Conference in Mexico City.

Last year, 420,000 babies were born HIV-positive, the large majority of them to HIV-infected mothers in sub-Saharan Africa, according to figures from the United Nations Joint Programme on HIV/AIDS. The centerpiece of public health programs in the developing world to stop mother-to-child transmission of HIV are both zidovudine (AZT) and nevirapine, which have been used as preventive tools in nearly 900,000 women and infants worldwide. The drugs are relatively inexpensive and easy to administer, and nevirapine is typically given as a single pill as the mother goes into labor and as a liquid to the baby just after birth. Use of the drug reduces the chance of HIV transmission by half, to about 13 percent. However, not all HIV-infected women have access to one or both of these drugs, especially in sub-Saharan Africa.

In addition, nevirapine has proven to be problematic. Previous studies have found that as many as 69 percent of HIV-positive mothers and as many as 80 percent of babies born infected, even after being given a single-dose of nevirapine without AZT, may develop nevirapine-resistant strains of the virus.

In the latest study, the Stanford scientists set out to better understand this problem.

They looked at a group of 32 HIV-positive pregnant women in Zimbabwe, where Katzenstein and his colleagues have had ongoing research and clinical programs in HIV/AIDS for more than a decade. The sub-Saharan African country has been hard hit by the virus, with an estimated 17 to 18 percent of young adults estimated to be infected. Among pregnant women, some 20 percent are thought to carry the virus.

In recent years, Zimbabwe has begun offering antiretroviral drugs to a limited number of infected patients, but at the time of the study, none of the women had been treated for their HIV. The only drug they received was the single dose of nevirapine when they went into labor, largely for the sake of their babies.

The researchers found that the drug persisted in the body for weeks, with more than half of the women having detectable levels in their blood within two weeks after delivery. Two-thirds had measurable levels in their breast milk at two weeks, the researchers found.

The longer the drug remains in the system, the more likely it is to promote development of mutations in the virus. Although none of the HIV-infected women carried drug-resistant strains of the virus at the outset of the study, at two months after birth RNA tests showed a third of them had drug-resistant virus in their blood. Sixty-five percent had drug-resistant strains in their breast milk as well, with the potential to pass this on to their babies through breastfeeding, a common mode of viral transmission.

The mothers who were most likely to develop resistant virus were those whose disease was more advanced as indicated by lower CD4 cell counts, the immune cells targeted by HIV, Kassaye said. With advanced HIV infection, these women are likely have more replicating virus, so they may be more prone to developing mutations that make the virus resistant to treatment, she said.

If these women had access to better, combination antiretroviral treatment to optimally suppress virus replication, they might be less likely to develop these hard-to-treat strains later, she said.

It reinforces the need to treat these women with combination therapy, thereby providing better prevention for the infant, while providing better treatment for the mother, Kassaye said. Public health efforts should continue to expand combination therapy so that mothers and babies aren't left vulnerable to drug resistance.

Combination therapy is a mix of drugs that is more expensive - and thus less accessible - in the developing world. In the United States, HIV-positive women receive a highly effective form of combination therapy that has reduced transmission of HIV from mother to infants to less than 2 percent.

Group of HIV patients with inadequate care

Mon, 04 Aug 2008 14:00:07 PST

( from http://www.rxpgnews.com ) Doctors who treat HIV-infected crack users refer to them as "the forgotten population." A study being presented at this week's International AIDS Conference in Mexico City reveals that these patients frequently lack outpatient health care, do not receive life-saving antiretroviral therapy and continue to engage in risky sexual behavior that likely contributes to HIV transmission.

Researchers interviewed 190 HIV-infected crack-using patients at Grady Memorial Hospital in Atlanta and Jackson Memorial Hospital in Miami over 14 months as part of an NIH/National Institute on Drug Abuse funded study.

One fourth of the group reported having unprotected sex in the last six months, half had not seen an HIV specialist in the last six months, and more than three fourths were not getting antiretroviral therapy, according to the interviews.

The five-year HOPE study (Hospital visit is an Opportunity for Prevention and Engagement) is a collaboration between the NIH funded Center for AIDS Research at Emory University School of Medicine and the NIH funded Developmental Center for AIDS Research at the University of Miami School of Medicine.

"At a time when life-saving medications are available to treat persons living with HIV, there continues to be a population of HIV-positive people who have fallen through the cracks," says Lisa Metsch, PhD, associate professor of epidemiology and public health at University of Miami School of Medicine. "Frequently, their only contact with the healthcare system is during a hospitalization."

Metsch is director of the University of Miami CFAR's behavior, social sciences and community outreach core and principal investigator for the HOPE study.

Previous studies of crack users in urban hospitals found that their drug use bars them from getting HIV-related care. Drug treatment experts say the short, intense nature of the crack high and lack of a methadone equivalent make crack users a unique group, on top of the chaotic lives they share with other drug users.

In addition, the study's interviews found that, compared with males, female HIV-infected crack users were more likely to report lack of HIV-related care (almost twice as likely) and recent unprotected sex (three times as likely), as well as annual income less than $5,000 and homelessness.

"We know that not being engaged in care and prevention services is not only bad for the individuals but is also bad for society, in that a substantial fraction of HIV-infected crack users engage in behavior that transmits the virus to others," says Carlos Del Rio, MD, professor of medicine and chief of medical services at Grady Memorial Hospital, co-director of the Emory Center for AIDS Research and co-principal investigator for the HOPE study.

The Emory and University of Miami researchers are testing the effectiveness of an eight-session intervention program that helps participants get into HIV care, teaches them about reducing risky sex practices and helps them into drug treatment if they are ready.

Del Rio says that the findings from this intervention study may be used to establish future interventions targeted to HIV-infected crack users to get them into care, keep them in care and allow them to benefit from care and prevention services available in HIV outpatient clinics.

"Hospitals like Grady and Jackson are doing the best they can in the face of a persistent problem, with limited resources," Del Rio says. "More needs to be done to address substance abuse and mental health in this population."

Antiretrovirals do not increase the risk for coronary atherosclerosis

Mon, 04 Aug 2008 13:07:48 PST

( from http://www.rxpgnews.com ) Antiretroviral drugs for HIV do not increase the risk for coronary atherosclerosis, a central risk factor for heart disease, according to a study led by the University of Pittsburgh Graduate School of Public Health to be published in the Aug. 8 issue of the journal AIDS and available online today. The results further suggest that antiretroviral therapy may offer men with HIV some protection against atherosclerosis – hardening of the arteries, caused in part by high levels of cholesterol, smoking and other lifestyle factors.

The study, part of the Multicenter AIDS Cohort Study (MACS) initiated in 1983, measured levels of coronary artery calcification (CAC) in nearly 950 HIV-positive and HIV-negative men by CT scanning completed between 2004 and 2006. Controlling for traditional atherosclerosis risk factors such as age, family history, smoking and blood pressure, the study team found that CAC scores were almost 60 percent lower in HIV-positive men who received highly active antiretroviral therapy (HAART) for more than eight years compared to HIV-negative men.

HAART, a course of treatment that involves the combination of three or more antiretrovirals, has been associated with an increase in cholesterol and other factors associated with atherosclerosis, leading some to question whether long-term use increases the risk of heart attack.

"When we first prescribed highly active antiretroviral therapy for HIV in 1995, we were concerned about how these drugs changed lipid levels in patients and whether they would increase atherosclerosis and ultimately lead to serious heart disease," said Lawrence Kingsley, Ph.D., study lead author and associate professor, Departments of Infectious Diseases and Microbiology and Epidemiology, University of Pittsburgh Graduate School of Public Health. "While some studies have found an association between these antiretroviral treatments and increased risk of cardiovascular disease, we believe our findings should reassure clinicians that using antiretroviral therapy over time does not appear to put patients at greater risk for coronary atherosclerosis and may, in fact, be more beneficial than we had initially thought."

The study also found that for both HIV-positive and HIV-negative men, older age was most strongly associated with the presence of coronary atherosclerosis. Smoking, lipid abnormalities and family history also played a role.

"This was not surprising since these are the major risk factors for atherosclerosis in the general population," said Dr. Kingsley. "The purpose of our study, however, was to investigate whether long-term HAART usage was a major risk factor."

"These results could be due, in part, to lower lipid values of HIV infected men prior to beginning antiretroviral therapy and high use of lipid-lowering drugs. The key is that controlling risk factors for atherosclerosis should be a priority," added Lewis Kuller, M.D., Dr.P.H, study co-author and professor of epidemiology, University of Pittsburgh Graduate School of Public Health.

Dr. Kingsley concluded, "What remains to be determined is whether use of the newest antiretroviral therapies confers an even better outcome and whether lipid-lowering therapies will further improve cardiovascular risk in the HIV-infected population. Our future research will address these questions."

Study highlights risky behavior, lack of care among HIV-infected crack users

Mon, 04 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Doctors who treat HIV-infected crack users refer to them as the forgotten population. A study being presented at this week's International AIDS Conference in Mexico City reveals that these patients frequently lack outpatient health care, do not receive life-saving antiretroviral therapy and continue to engage in risky sexual behavior that likely contributes to HIV transmission.

Researchers interviewed 190 HIV-infected crack-using patients at Grady Memorial Hospital in Atlanta and Jackson Memorial Hospital in Miami over 14 months as part of an NIH/National Institute on Drug Abuse funded study.

One fourth of the group reported having unprotected sex in the last six months, half had not seen an HIV specialist in the last six months, and more than three fourths were not getting antiretroviral therapy, according to the interviews.

The five-year HOPE study (Hospital visit is an Opportunity for Prevention and Engagement) is a collaboration between the NIH funded Center for AIDS Research at Emory University School of Medicine and the NIH funded Developmental Center for AIDS Research at the University of Miami School of Medicine.

At a time when life-saving medications are available to treat persons living with HIV, there continues to be a population of HIV-positive people who have fallen through the cracks, says Lisa Metsch, PhD, associate professor of epidemiology and public health at University of Miami School of Medicine. Frequently, their only contact with the healthcare system is during a hospitalization.

Metsch is director of the University of Miami CFAR's behavior, social sciences and community outreach core and principal investigator for the HOPE study.

Previous studies of crack users in urban hospitals found that their drug use bars them from getting HIV-related care. Drug treatment experts say the short, intense nature of the crack high and lack of a methadone equivalent make crack users a unique group, on top of the chaotic lives they share with other drug users.

In addition, the study's interviews found that, compared with males, female HIV-infected crack users were more likely to report lack of HIV-related care (almost twice as likely) and recent unprotected sex (three times as likely), as well as annual income less than $5,000 and homelessness.

We know that not being engaged in care and prevention services is not only bad for the individuals but is also bad for society, in that a substantial fraction of HIV-infected crack users engage in behavior that transmits the virus to others, says Carlos Del Rio, MD, professor of medicine and chief of medical services at Grady Memorial Hospital, co-director of the Emory Center for AIDS Research and co-principal investigator for the HOPE study.

The Emory and University of Miami researchers are testing the effectiveness of an eight-session intervention program that helps participants get into HIV care, teaches them about reducing risky sex practices and helps them into drug treatment if they are ready.

Del Rio says that the findings from this intervention study may be used to establish future interventions targeted to HIV-infected crack users to get them into care, keep them in care and allow them to benefit from care and prevention services available in HIV outpatient clinics.

Hospitals like Grady and Jackson are doing the best they can in the face of a persistent problem, with limited resources, Del Rio says. More needs to be done to address substance abuse and mental health in this population.

UGA researchers win $9.2 million stem cell grant from NIH

Mon, 04 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A research group led by Stephen Dalton, professor and Georgia Research Alliance Eminent Scholar of Molecular Biology at the University of Georgia, has been awarded $9.2 million as part of a major new research grant by the National Institute of General Medical Sciences, part of the National Institutes of Health.

Dalton's group, headquartered in the department of biochemistry and molecular biology, will address the molecular underpinnings of the early steps that stem cells take in becoming specialized cell types. The scientists will also seek to identify the genetic and protein modification patterns that accompany this process of differentiation.

The new grant in UGA's Franklin College of Arts and Sciences is part of $27 million in funding awarded to the University of Wisconsin, UCLA and UGA that NIGMS has added to its ongoing effort to uncover the basic biology of human embryonic stem cells.

Our program will offer training for scientists seeking to gain expertise in the specialized techniques needed to work with embryonic stem cells and will serve as a source of reagents, technical support and methodology development, said Dalton, who is also a Georgia Cancer Coalition Distinguished Scholar and a member of UGA's developmental biology program.

The results of all three new programs are expected to deepen existing knowledge of the unique properties of stem cells and will be important to researchers trying to develop stem-cell-based therapies.

This program project grant is important for a number of reasons, said David Lee, UGA vice president for research. Certainly it highlights the expertise in stem cell biology and glycomics at the University of Georgia. But perhaps more important, it is cleverly designed to promote stem cell research throughout the Southeast. One of the core facilities funded by the grant is specifically tasked with developing new stem cell technologies that will be disseminated to researchers across the region via the new Southeast Stem Cell Consortium, which Professor Dalton chairs. We are extremely pleased by the leadership provided by Dr. Dalton in an area that offers so much promise for human health.

Dalton's position as a leader in stem-cell research has been solidified with the recent establishment of the Southeast Stem Cell Consortium. The consortium has strong interests in the basic biology of stem cells, their utility as a model for studying mammalian development and their potential as a cell source to develop therapies for degenerative disease and repair of chronic injury. Focus areas include diabetes, cardiovascular disease, spinal cord injury and neurodegenerative disease.

This is an innovative program that focuses on an understudied area of stem cell biology, said Marion Zatz, Ph.D., who oversees stem cell grants at the National Institute of General Medical Sciences of the National Institutes of Health. By looking at how proteins are modified by sugar molecules as stem cells differentiate, Dalton's team could help us understand how the many distinct cell types in our bodies are formed.

Dalton's research group at UGA focuses on the uses of stem cells in understanding diabetes and cardiovascular disease. One current project involves finding ways to use stem cells to repair the human heart.

The heart is an organ that doesn't repair itself, said Dalton. But we're studying a resident population of stem cells that have the capability of dividing and turning into cardiac cells. Theoretically, they could be used to help the heart repair itself after a heart attack.

The new programs join an NIGMS effort launched in 2003 to explore the basic molecular and genetic features of human embryonic stem cells. Prior to the latest awards, the initiative has included six exploratory centers, two multidisciplinary research programs and several independent research projects and supplements.

New male circumcision device for HIV prevention studied by NewYork-Presbyterian/Weill Cornell

Fri, 01 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (July 31, 2008) -- With the recent endorsement by the World Health Organization (WHO) and scientists worldwide of adult male circumcision as an important strategy for HIV prevention, there is increased urgency to develop safe and cost-effective circumcision services. This is especially the case in Africa where HIV/AIDS continues to spread at an epidemic rate.

Studying this method are Dr. Marc Goldstein and physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, who are evaluating an innovative circumcision device developed in China and will initiate a study of the device in Africa in the coming months.

The device, named the ShangRing after its inventor, Mr. Jian-Zhong Shang, consists of two concentric plastic rings that sandwich the foreskin, allowing it to be cut away without suturing and with minimal bleeding. Performed in a clinic under local anesthesia, the procedure takes less than five minutes, compared with approximately 20 to 30 minutes for a traditional free hands circumcision that requires suturing. The patient returns in one week for device removal.

Circumcision with this technique promises to be faster, safer and more acceptable to patients than conventional surgical circumcision methods, says Dr. Goldstein, the study's principal investigator. He is urologist and specialist in reproductive medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, the Matthew P. Hardy Distinguished Professor of Reproductive Medicine and Urology at Weill Cornell Medical College, and senior scientist at The Population Council, Center for Biomedical Research, located on the campus of The Rockefeller University.

The hope is that with these advantages, circumcision will become more commonplace (currently only between 15 and 50 percent of sub-Saharan males are circumcised). Its advantages include reduced risk of a variety of sexually transmitted diseases (STDs), notably HIV.

Circumcision is the only new HIV prevention method to demonstrate consistent efficacy in randomized controlled trials, notes co-principal investigator Dr. Philip S. Li, associate research professor of urology and reproductive medicine and director of microsurgical research and training at the Center for Male Reproductive Medicine and Microsurgery at Weill Cornell Medical College.

Three randomized controlled trials in Kenya, Uganda and South Africa reported a protective effect (up to 60 percent) of circumcision against HIV infection. The World Health Organization, the Joint United Nations Programme on HIV/AIDS (UNAIDS), and other global reproductive health organizations such as EngenderHealth have recognized circumcision as an important method to reduce HIV infection.

The ShangRing has been used to circumcise several thousand Chinese men since 2005. Preliminary reports of 1,200 patients indicate good results with minimal complications. The ShangRing, with 15 patents pending in 85 countries, is currently available only in China. FDA evaluation is under way.

The beauty of this device is its simple, innovative design, says Dr. Howard Kim, a fellow in male reproductive medicine and microsurgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and member of the Weill Cornell team that traveled to China to learn this new technique. Although many male circumcision devices are available, they have not gained widespread acceptance due to high complication rates or difficulties with surgical technique.

Even non-physician health care providers will be able to learn this procedure to safely perform circumcisions in resource-poor regions, adds Dr. Richard Lee, a chief resident in urology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and another member of the China team.

The NewYork-Presbyterian/Weill Cornell team, in collaboration with the nonprofits EngenderHealth and The Population Council, are planning a small pilot study in Nyanza, Kenya, to test efficacy, safety and acceptability of the technique. Local health providers who perform circumcisions in a clinical setting will be recruited and trained in the procedure by the NewYork-Presbyterian/Weill Cornell team. The pilot study is expected to be followed by a multicenter clinical trial that will compare the ShangRing technique to traditional circumcision methods.

Male circumcision has been performed as far back as ancient Egypt, and the practice has continued through the ensuing centuries for religious, cultural and sociopolitical reasons. Performing circumcision for potential health benefits gained momentum in the 19th century with the advent of anesthesia and the initial epidemiological studies demonstrating lower rates of venereal diseases in circumcised men. Recent studies have shown that circumcised men are at significantly lower risk of urinary tract infections and sexually transmitted infections such as syphilis and chancroid. Additional studies point to lower risk of invasive penile carcinoma, gonorrhea and chlamydia (in female partners).

ASM and FIND to partner on strengthening infectious disease diagnosis in developing nations

Thu, 31 Jul 2008 04:00:00 PST

( from http://www.rxpgnews.com ) The American Society for Microbiology (ASM) and the Foundation for Innovative New Diagnostics (FIND) have signed a Memorandum of Understanding today confirming their agreement to work in partnership for projects aimed at strengthening infectious disease diagnosis and service integration in resource-poor and transitional countries.

The collaboration between the ASM and FIND will focus on strengthening the foundation for infectious disease diagnosis in resource-poor nations, providing novel diagnostics and laboratory expertise for tuberculosis and other infectious diseases that are appropriate to the unique circumstances found in developing nations, says Steven Specter, Chair of the ASM's International Laboratory Capacity Building Committee.

The memorandum of understanding signed by the ASM and FIND arises from a pilot project that the two organizations have been conducting in Cote d'Ivoire since April 2008. In the pilot collaboration, FIND is developing and providing rapid, accurate and affordable tuberculosis diagnostic tests that can be effectively deployed in resource poor areas while the ASM is sending experts in clinical microbiology to provide training and technical assistance in the implementation of these new tests.

We expect our partnership to reinforce the expansion and further development of quality-assured laboratory services as part of a larger framework of health system strengthening within resource-poor settings. Combating poverty-related infectious diseases with the development and rapid introduction of new diagnostic tests where they are most needed is why partnerships like the one between FIND and ASM are extremely important, says Giorgio Roscigno, CEO of FIND.

The WHO estimates that 2 billion people, or approximately one third of the world's population, are infected with the bacteria that cause tuberculosis. Africa represents 28% of all tuberculosis cases and has the highest infection rate per capita. Tuberculosis is a leading cause of death among people living with HIV/AIDS and most of the world's 200,000 HIV/TB deaths occur in Africa.

One of the primary challenges is that modern diagnostic tools for tuberculosis in industrialized countries are not suited to the infrastructure of resource poor nations where in some cases just getting reliable electricity is a problem. New, reliable diagnostics that can be effectively implemented in developing nations, as well as the expertise to use them, are urgently needed.

FIND is prioritizing tests that can be adopted at the lowest level of the health system, where a large number of patients first seek care. The technologies targeted for each level are intended to match the human resources available and the degree of complexity of the diagnostic question. Some of the diagnostic tools expected to be introduced into control programs will be incremental improvements on existing technologies while others will be radically new.

ASM, through its International Laboratory Capacity Building program, is ensuring the quality-assured implementation of new and existing diagnostic tools in resource-limited countries through onsite training and technical assistance. For this purpose, ASM is strengthening clinical microbiology laboratories by mobilizing its members to build human resource capacity for diagnosis of tuberculosis and other infectious diseases.

The memorandum of understanding is expected to serve as the beginning of a close collaboration between the ASM and FIND towards maximizing their complementary strengths and contributions to global health efforts.

Combination anti-retroviral therapy increases life expectancy by greater than 13 years

Fri, 25 Jul 2008 23:29:47 PST

( from http://www.rxpgnews.com ) The life expectancy for patients with human immunodeficiency virus (HIV) has increased by more than 13 years since the late 1990s thanks to advancements in antiretroviral therapy, according to researchers at the University of Alabama at Birmingham (UAB) and Simon Fraser University in Vancouver, British Columbia.

Improved survival has led to a nearly 40 percent drop in AIDS deaths among 43,355 HIV-positive study participants in Europe and North America, bolstering the call for improved anti-HIV efforts worldwide, the study authors said.

The study is published in the British medical journal The Lancet. It was compiled by The Antiretroviral Therapy Cohort Collaboration, which includes UAB, Simon Fraser University and more than a dozen other research sites around the world.

The authors looked at changes in life expectancy and mortality among the 43,355 HIV patients taking a cocktail of drugs called combination antiretroviral therapy (cART). Data was compiled from a total of 14 studies in Europe and North America.

"Since their introduction in 1996 cART regimens have become more effective, better tolerated and easier to follow," said Michael Mugavero, M.D., an assistant professor in UAB's Division of Infectious Diseases and a co-author on the study.

"We are now seeing the benefits of years of research, hard work and efforts to make these medications widely available. This has led to dramatic improvements in life expectancy, but patients who start cART with more advanced HIV infection do not have the same level of benefit," Mugavero said.

The new Lancet study found cART yielded a 13.8-year life-expectancy increase - from 36.1 years in study participants who began therapy during the 1996-1999 period to 49.9 years in participants who began therapy during the 2003-2005 period.

Despite the good results, the study found life expectancy for HIV patients is far lower on average than the general population, which includes all those with other chronic illnesses. For example, an HIV-positive patient starting cART at age 20 will live to 63, about 20 years shorter than the average life span of non-infected adults.

With nearly half of all patients diagnosed with advanced HIV infection, the life expectancy benefits of cART are not fully realized, said Mugavero and lead study author Robert Hogg, Ph.D., of Simon Fraser University. Improved AIDS testing and increased access to care is needed.

HIV-I knocks out immune system faster than thought

Sat, 19 Jul 2008 13:37:35 PST

( from http://www.rxpgnews.com ) Washington, July 19 - The HIV-I virus virtually knocks out the immune system much faster than previously thought.

The window of opportunity for successful intervention may be only a matter of days - not weeks - after transmission, according to scientists of Duke University Medical Centre.

The finding may compound the problem of the challenge of designing an effective HIV/AIDS vaccine. But it has also yielded a blueprint for what a successful vaccine should look like, and moreover, when such a vaccine would need to work.

Until now, scientists believed that the window of opportunity for intervention lasted three to four weeks between transmission and the development of an established pool of infected CD4 T cells. HIV-1 cripples the immune system by invading and killing CD4 T cells, key infection-fighters in the body.

'But this new study shows that HIV-I does a lot of damage to the immune system very early ... and now we feel that the opportunity to intervene most effectively may range from about five to seven days after infection,' said Barton Haynes, co-author of the study and director, Duke Centre for HIV/AIDS Vaccine Immunology -.

Haynes said the findings suggest that an optimal vaccine strategy would have to pack a double punch: First, establishing as much immunity as possible before infection, much as classic vaccines do, and then following a few days later with a mechanism to provoke a strong, secondary, broad-based antibody response.

'Vaccine candidates to date have pretty much followed a single strategy. Now we know that we need to activate multiple arms of the immune system and we have a better idea of when to do it.'

The conclusion is based on a study of 30 people who were newly-infected with HIV-I. Plasma from these individuals was sampled every three days for several months - before, during, and after the 'ramp-up' phase of infection, when HIV-I is multiplying rapidly and heading toward its peak viral load.

In measuring the levels of four products of CD4 T cell death during this period in these samples, they were able to track and establish a timetable of the virus's destructive path.

These findings will appear in the August issue of the Journal of Virology.

With $2M NIH grant, FSU becomes 1 of world's top imaging centers

Wed, 16 Jul 2008 04:00:00 PST

( from http://www.rxpgnews.com ) TALLAHASSEE, Fla. -- At Florida State University, the collective strength of biomedical research and the scientists who lead it has earned a $2 million High-End Instrumentation (HEI) grant from the National Institutes of Health (NIH). The one-year award will help FSU buy a state-of-the-art robotic electron microscope to advance cutting-edge studies of HIV/AIDS, heart disease, hypertension and cancer.

FSU will have $4.8 million in total funding after it matches the $2 million NIH award with $2.8 million from monies the university has set aside specifically to support research.

Installing this groundbreaking technology will place us among the very top imaging centers in the world, said FSU College of Arts and Sciences Dean Joseph Travis. He declared the competition unbelievably tough for HEI grants, which come from the National Center for Research Resources (NCRR), a part of NIH that provides laboratory scientists and clinical researchers with the tools and training they need to understand, detect, treat and prevent a wide range of diseases.

For its $4.8 million investment, FSU will get a fully automated cryo-electron microscope that provides rapid, 3-D imaging of frozen specimens around-the-clock via remote operation, then transmits them over the Internet. In addition to significantly speeding the collection of crucial data, researchers in biology and chemistry at FSU and colleagues at other institutions will get unprecedented views of -- and 24/7 access to -- the intricate interactions of individual proteins and molecular machines within the living cells of complex biological structures.

Currently, the world's only working installation of this microscope is in Germany, Travis said. In the U.S., FSU will have one of only four. The others will be installed at NIH itself; the University of California-Berkeley; and the National Center for Microscopy and Imaging Research at the University of California-San Diego -- all acknowledged as the best in the nation for structural biology and structural biological imaging. FSU soon will have capabilities unmatched by all but a few institutions in the nation.

Travis noted that it's extremely rare to see an HEI grant, especially such a large one, awarded to a single group of investigators; typically awards of that type go to national centers or nationwide facilities serving multiple groups. It's quite a testament to the scientific ingenuity of the group that will comprise the instrument's primary users, the importance of the work they do, and the commitment FSU has made to their research areas, he said.

Innovative biomedical research requires frequent access to the newest and most advanced technology, said Barbara Alving, M.D., director of NCRR. Such tools play key roles in the study of disease and the fundamental mechanisms of biological function, ultimately leading to new advances and treatments for diseases.

Expected to stand 16 feet high and weigh 1.7 tons, the new microscope will serve as a crucial tool to the cadre of FSU scientists who will share it once required renovations to the building in which it will be housed are completed in 2009.

This instrument will be cutting-edge in several ways, said biological science Professor Kenneth Taylor, the principal investigator on FSU's award-winning grant application.

Not only is it robotic, collecting data continually without operation attention, in fact it can only be operated remotely, Taylor said. There's no conventional 'binocular' for the user to view the image. What's more, the microscope can be operated and the images viewed by anyone in the U.S. with high-speed Internet capability and the required, specially designed workstation.

Five major FSU research projects helped secure the NIH-NCRR grant for 2008.

Among them is a cell adhesion study led by Taylor, a member of the unique interdisciplinary FSU Institute of Molecular Biophysics (

Increased diabetes risk in HIV -positive children; increased cholesterol with some treatments

Tue, 15 Jul 2008 11:45:12 PST

( from http://www.rxpgnews.com ) UC Davis researchers have found, that despite results to the contrary in adults, average cholesterol profiles in young children with HIV do not worsen when they are put on highly active antiretroviral therapy (HAART)--but only when certain combinations of drugs are used. The researchers also found that children beginning or switching to HAART also showed an increase in insulin resistance, potentially raising their risk of developing diabetes later in life.

"These children are facing a lifetime of potential complications, not just from their HIV infection, but from the drugs used to treat it," said Caroline Chantry, associate professor of pediatrics. The study is the largest to date looking at metabolic disruption caused by HIV and associated treatment in children before puberty. "We need to know now if these children will be at greater risk of developing heart disease or diabetes so that we can improve treatment and focus on prevention," Chantry said.

The current study was published online by Pediatrics on June 2.

The good news for patients, based on the current study, is that increasing CD4 T-cell counts--a measure of immune function used to gauge success of HAART--results in improvements in cholesterol levels. Their risk of diabetes, however, remains a concern because the children involved in the study showed increases in their bodies' resistance to the action of insulin, the hormone responsible for stabilizing blood glucose levels.

"The values were not so high as to diagnose them with diabetes, but insulin resistance is a risk factor for developing the disease," Chantry said. The issue will require further study, she added.

Chantry and her colleagues also discovered that improved lipid profiles paralleled improved sensitivity to growth hormone. This provides a clue to a possible cause of abnormal cholesterol in the infected children that could eventually lead to better treatment or prevention strategies. Children with HIV often suffer from stunted growth as a result of growth hormone resistance.

There is other good news with respect to the study's cholesterol findings, Chantry said. Physicians can further reduce their pediatric patients' risk of developing high cholesterol by simply changing the combination of drugs they are given as part of HAART. Children in the study had worse cholesterol profiles (lower levels of HDL, the so-called "good" cholesterol and a higher total to HDL cholesterol ratio) when a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor were used in combination, but not when either was used alone.

Previous studies had shown that adults and teenagers on HAART commonly showed increases in cardiovascular risk because of increased LDL levels and in insulin resistance. Chantry and her colleagues decided to take a look at these metabolic disturbances in younger patients.

The 97 children included in this study were part of the Pediatric AIDS Clinical Trials Group Protocol 1010, a multi-state 48-week observational study. They ranged in age from less than one-month to less than 13 years and had predominantly mild-to-moderate disease. To be included, the children had to either be starting HAART for the first time or changing treatment because other therapies had failed.

Blood samples were taken during the study. Fasting cholesterol, glucose, insulin and CD4 T-cells were among the blood levels measured. To analyze the data, each child was matched for age, gender and race/ethnicity with data from children in the National Health and Nutrition Examination Survey.

Researchers found that initiation or change in HAART in these children was associated with significant increases in T-cell counts, both bad (LDL) and good cholesterol (HDL) measures, sensitivity to growth hormone, and insulin resistance.

"We were very surprised to find out that overall cardiovascular risk does not increase for these children starting or switching HAART," Chantry said. The results showed that both HDL (good) and LDL (bad) cholesterol, increased, but the good more so than the bad. "There were some good changes and some not-so-good changes, but the net effect was no increased risk," she added, "and some children actually improved."

Doctors use a variety of combinations in HAART that can include one or the other or both of the classes of drugs known as protease inhibitors and non-nucleoside reverse transcriptase inhibitors. "The combinations that have both classes were worse for the patients in terms of lipid profiles," Chantry said. "Either one of these classes along with other types antiretrovirals is better than both together."

Keeping children with HIV healthy for as long as possible means looking at the way they are affected by the drugs used to treat them, Chantry said. "Children are not little adults. We are never sure until we look whether or not what is medically going on in adults is also going on in children."

New HIV browser gives researchers access to valuable data from vaccine trials

Thu, 29 May 2008 04:00:00 PST

( from http://www.rxpgnews.com ) SANTA CRUZ, CA--A new HIV data browser developed by the University of California, Santa Cruz, and the nonprofit organization Global Solutions for Infectious Diseases (GSID) will give researchers access to a wealth of data collected during clinical trials of an AIDS vaccine. Although the vaccine did not succeed in preventing infections, the clinical trial generated a huge amount of valuable data for researchers studying how the virus evolves and causes new infections.

Modeled on the UCSC Genome Browser, the GSID HIV Data Browser is the brainchild of Phillip Berman, professor and chair of biomolecular engineering in UCSC's Baskin School of Engineering. Berman helped oversee the clinical trials, which ended in 2003, when he was senior vice president for research and development at VaxGen, the company that developed the vaccine and conducted Phase III clinical trials in North America, Europe, and Thailand.

After the trials concluded, I spent a couple of years trying to think what was the most important thing I could do for HIV research, Berman said. I concluded it was using new technology to preserve the data from these clinical trials and present it in a form useful to the scientific community.

In 2004, Berman cofounded GSID, based in South San Francisco and dedicated to combining knowledge and expertise from the biotechnology industry and the public health sector to address infectious disease problems in the developing world. He joined the UCSC faculty in 2006.

Despite the fact that the vaccine trial didn't work, a huge amount of useful information was obtained, Berman said. The North American trial included about 60 different clinical sites in North America and one site in the Netherlands. Of particular value to researchers are the genetic sequences of the viruses that infected participants during the trial.

The trial represented the only up-to-date broad survey of virus sequences from new infections that had ever been carried out, Berman said. Every time there was a new infection in the vaccine or placebo group, the virus was sequenced. The sequence information provides the best picture we have about what the immune system sees when there is a new infection.

This is important, Berman said, because other major repositories of HIV sequence data are not annotated for the time after infection, the clinical status of the patient, or the histories of the specimens sequenced. That limits their usefulness for studying such a rapidly evolving virus.

HIV is highly mutable and evolves in response to attacks by the immune system. As a result, HIV isolated from a patient years after the initial infection is genetically different from the virus that caused the infection in the first place. A vaccine should target the most infectious form of the virus, Berman said. Yet all the vaccines tested so far have been based on viruses isolated from patients with longstanding infections.

A current hypothesis in HIV vaccine research is that the antigenic structures of HIV viruses that mediate new infections differ from those recovered from people long after infection, Berman explained. The specimens in this set represent the largest group from new infections that has ever been collected.

Besides viral genome-sequence data, the database links to a repository of preserved specimens (blood samples and cells) that researchers can access from GSID and the National Insitutes of Health (NIH) for further study.

This is the first time that an HIV sequence database has been linked to a specimen repository and a database of clinical information, Berman said. These clinical specimens are longitudinal, collected from the same person during a two-year follow-up period. This will allow investigators to study the evolution of the virus and the evolution of the immune response and clinical outcomes.

At UCSC, Berman teamed up with the Genome Browser group to develop a browser for the sensitive clinical data collected during the vaccine trial. Jim Kent, associate research scientist for the UCSC Genome Browser and principal investigator on the project, said it was the first time his group had worked with data from participants in a clinical trial.

This data must be handled differently and great care taken with confidentiality, Kent said. We learned from this project how to build the infrastructure to cope with that. This will be useful for other medical projects, such as cancer genomics, in the future.

Fan Hsu, director of proteomics for the UCSC Genome Browser, said the emphasis on security was very different from past projects. Before, everything we have worked on is totally open, totally public. With the GSID project, only authorized users can access the data, so we needed to set up special controls, Hsu said.

How to display the very large number of HIV sequences on the browser was another challenge. Our original genome browser has only one reference genome. For this HIV database, we have about 350 infected people and more than 1,000 sequences, he said.

Hsu and software developer Galt Barber adapted the genome browser software to accommodate the large number of HIV sequences and the data security along with interactive selection criteria for viewing the data. As the project evolved, Hsu also coordinated the transfer of the software to GSID. The UCSC team, which also included Erich Weiler, Robert Kuhn, and Ann Zweig, worked nights and weekends to bring the new browser online.

The resulting GSID HIV Data Browser is a customized version of the UCSC Genome Browser. It provides researchers with searchable demographic and clinical data from volunteers who became HIV infected during the VaxGen clinical trial. The browser allows users to align viral sequences with one another and with reference or consensus sequences.

This is something where the university can make a difference, because the private sector is not so interested in vaccines; they're not so profitable, Kent said. There is very little economic incentive to develop an AIDS vaccine, but there is a tremendous humanitarian incentive.

Kent hopes that just as the UCSC Genome Browser has continued to build the collaborative nature of the genomics research community, this HIV data browser will help motivate the AIDS research community to work together and pool their data.

Vaccine development efforts have been repeatedly frustrated. An HIV vaccine candidate developed by the pharmaceutical company Merck recently failed in clinical trials cosponsored by NIH. The recent failure of the Merck HIV vaccine has thrown the field into turmoil, Berman said. All the best ideas for an HIV vaccine in the past 20 years have failed. The information in this database is now more critical than anyone could have imagined. It tells us what's being transmitted.

The next phase of the HIV browser project involves releasing the sequence data from infected participants in the Phase III clinical trial that VaxGen conducted in Thailand.

In the future, the database will be expanded to allow associations between virus sequences, clinical data, immune response data, and host genetics, Berman said. We hope to eventually include data from other HIV vaccine trials sponsored by the NIH, private companies, and other HIV vaccine research organizations.

The formation of a HIV particle- imaged

Mon, 26 May 2008 04:39:30 PST

( from http://www.rxpgnews.com ) A mapmaker and a mathematician may seem like an unlikely duo, but together they worked out a way to measure longitude – and kept millions of sailors from getting lost at sea. Now, another unlikely duo, a virologist and a biophysicist at Rockefeller University, is making history of their own. By using a specialized microscope that only illuminates the cell’s surface, they have become the first to see, in real time and in plain view, hundreds of thousands of molecules coming together in a living cell to form a single particle of the virus that has, in less than 25 years, claimed more than 25 million lives: HIV.

This work, published in the May 25 advanced online issue of Nature, may not only prove useful in developing treatments for the millions around the globe still living with the lethal virus but the technique created to image its assembly may also change the way scientists think about and approach their own research.

“The use of this technique is almost unlimited,” says Nolwenn Jouvenet, a postdoc who spearheaded this project under the direction of HIV expert Paul Bieniasz and cellular biophysicist Sandy Simon, who has been developing the imaging technique since 1992. “Now that we can actually see a virus being born, it gives us the opportunity to answer previously unanswered questions, not only in virology but in biology in general.”

Unlike a classical microscope, which shines light through a whole cell, the technique called total internal reflection microscopy only illuminates the cell’s surface where HIV assembles. “The result is that you can see, in exquisite detail, only events at the cell surface. You never even illuminate anything inside of the cell so you can focus on what you are interested in seeing the moment it is happening,” says Simon, professor and head of the Laboratory of Cellular Biophysics.

When a beam of light passes through a piece of glass to a cell’s surface, the energy from the light propagates upward, illuminating the entire cell. But when that beam is brought to a steeper angle, the light’s energy reflects off the cell’s surface, illuminating only the events going on at its most outer membrane. By zeroing in at the cell’s surface, the team became the first to document the time it takes for each HIV particle, or virion, to assemble: five to six minutes. “At first, we had no idea whether it would take milliseconds or hours,” says Jouvenet. “We just didn’t know.”

“This is the first time anyone has seen a virus particle being born,” says Bieniasz, who is an associate professor and head of the Laboratory of Retrovirology at Rockefeller and a scientist at the Aaron Diamond AIDS Research Center. “Not just HIV,” he clarifies, “any virus.”

To prove that what they were watching was virus particles assembling at the surface (rather than an already assembled virion coming into their field of view from inside the cell), the group tagged a major viral protein, called the Gag protein, with molecules that fluoresce, but whose color would change as they packed closer together. Although many different components gather to form a single virion, the Gag protein is the only one necessary for assembly. It attaches to the inner face of the cell’s outer membrane and when enough Gag molecules flood an area, they coalesce in a way that spontaneously forms a sphere.

Simon, Bieniasz and Jouvenet found that the Gag molecules are recruited from the inside of the cell and travel to the cell’s surface. When enough Gag molecules get close and start bumping into each other, the cell’s outer membrane starts to bulge outward into a budding virion and then pinches off to form an individual, infectious particle. At this point, the researchers showed that the virion is a lone entity, no longer exchanging resources with the cell. By using tricks from optics and physiology, they were able to watch the steps of viral assembly, budding, and even scission off the cell surface. With such a view they can start to describe the entire lifeline in the birth of the virus.

“I think that you can begin to understand events on a different level if you actually watch them happen instead of inferring that they might occur using other techniques,” says Bieniasz. “This technique and this collaboration made that possible.”

Scientists identify key roadblock to gene expression

Thu, 08 May 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A team of scientists has provided, for the first time, a detailed map of how the building blocks of chromosomes, the cellular structures that contain genes, are organized in the fruit fly Drosophila melanogaster. The work identifies a critical stop sign for transcription, the first step in gene expression, and has implications for understanding how the AIDS virus regulates its genes. The findings will be published in the 15 May 2008 issue of the journal Nature.

The scientists found that nucleosomes--chromosomal building blocks made up of proteins around which DNA is coiled--occur at precise locations along genes that are actively undergoing transcription. They also showed that RNA polymerase--the enzyme that reads genes as the first step in making proteins--is stopped at the first nucleosome, where it remains idle until it is directed to continue moving forward. This discovery is important because nucleosomes are barriers to transcription and we now are seeing the impact of nucleosome organization on RNA polymerase, said lead investigator B. Franklin Pugh, professor and Willaman Chair in Molecular Biology at Penn State University.

Using state-of-the-art ChIP-sequencing, a genome-mapping tool provided by collaborator Stephen S. Schuster, Penn State professor of biochemistry and molecular biology, and computational predictions developed by collaborators Ilya Ioshikhes, an assistant professor at Ohio State University, and Istvan Albert, a research assistant professor of bioinformatics at Penn State, the scientists precisely mapped the locations of hundreds of thousands of nucleosomes. The scientists then compared these maps to the team's earlier maps of the baker's yeast Saccharomyces cerevisiae, revealing that evolution has organized nucleosomes differently in simple life forms compared to more complex organisms like the fruit fly.

In yeast, a nucleosome sits on top of the transcription start site, so RNA polymerase must contend with that nucleosome as soon as it begins to transcribe the gene. In contrast, nucleosomes are positioned further downstream in fruit flies, so transcription starts but then soon pauses at the first nucleosome the RNA polymerase encounters. This pause is maintained until chemical signals from the cell cue the removal of the nucleosome and encourage the RNA polymerase to continue along its path, said key collaborator David S. Gilmour, professor of molecular and cellular biology at Penn State and an expert on the pausing of RNA polymerase.

A year ago, we could name about 10 genes that work this way. Now, we know of 1,000 in flies alone and we suspect there could be many more in humans, said Gilmour. Even HIV genes have a paused RNA polymerase. Release of this pause may be key to activating HIV replication of otherwise latent viruses. Taking advantage of this new understanding might enable the development of more effective anti-viral drugs, he said.

The bottom line is that we need to know how the expression of genes is regulated in order to understand the underpinnings of most human diseases, and these findings take us one step closer, said Pugh.

Molecular espionage shows a single HIV enzyme's many tasks

Wed, 07 May 2008 04:00:00 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, Mass. -- Using ingenious molecular espionage, scientists have found how a single key enzyme, seemingly the Swiss army knife in HIV's toolbox, differentiates and dynamically binds both DNA and RNA as part of the virus' fierce attack on host cells. The work is described this week in the journal Nature.

The enzyme, reverse transcriptase (RT), is already the target of two of the three major classes of existing anti-HIV drugs. The new work, using single-molecule fluorescent imaging to trace RT's activity in real time, not only reveals novel insights into how this critical viral enzyme functions, but also clarifies how some of the anti-HIV pharmaceuticals work.

The research team, at Harvard University and the National Cancer Institute, was led by Xiaowei Zhuang at Harvard and Stuart Le Grice at NCI. Elio A. Abbondanzieri at Harvard and Gregory Bokinsky, formerly at Harvard and now at the Lawrence Berkeley National Laboratory, are lead authors.

Our experiments allowed us, for the first time, a peek at how individual RT molecules interact with the HIV genome, says Zhuang, professor of chemistry and chemical biology and of physics in Harvard's Faculty of Arts and Sciences, as well as an investigator with the Howard Hughes Medical Institute. We found that RT binds RNA and DNA primers with opposite orientations and that RT's function is dictated by this binding orientation.

HIV begins its assault by injecting its single-stranded RNA into a host cell. Three subsequent steps are all mediated by RT: The viral RNA is converted into single-stranded DNA, the single-stranded DNA is replicated into double-stranded DNA, and the original viral RNA is degraded. Another enzyme mediates the final step of the genome conversion, where the viral double-stranded DNA is inserted into the host's DNA, allowing it to take advantage of the host's genetic machinery to replicate and propagate itself.

Using their molecular probe to spy on this process, Abbondanzieri and colleagues traced RT's multitasking skill to its dynamic active sites, which allow it to bind and process RNA as well as single- or double-stranded DNA.

Remarkably, RT can spontaneously flip between these two opposite orientations on DNA and RNA to facilitate two distinct catalytic activities, says Abbondanzieri, a postdoctoral researcher in Harvard's Department of Chemistry and Chemical Biology. These flipping motions, which have never before been seen in a protein-nucleic acid complex, can be likened to a nanoscale version of a gymnastics routine on a pommel horse.

The 180-degree flipping of RT is regulated by nonnucleoside RT inhibitors (NNRTIs), a major class of anti-HIV drugs. Abbondanzieri and coworkers observed NNRTIs inhibiting HIV activity by accelerating RT's flipping between its two active sites, hindering the enzyme's ability to convert single-stranded DNA to double-stranded DNA.

Stanford researchers synthesize compound to flush HIV out of hiding

Thu, 01 May 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Any hunter will tell you that when your quarry goes into hiding, you have to flush it out to get a good shot at it. Such is the case with HIV, the virus that causes AIDS.

Though antiretroviral cocktails can target an active infection, they cannot get at the virus when it retreats inside the host's T cells, where it may lie dormant for decades, waiting for an opportunity to burst forth in a fresh round of infection. What HIV hunters need is a good bird dog.

Now, Stanford chemist Paul Wender and his coworkers have found a way to synthesize better bird dogs, agents that can be tailored to flush HIV out into the open where the immune system and antiretroviral therapies can destroy it. Wender is senior author of a paper about the research in the May 2 issue of Science.

We're not sure how far this will go, but certainly, from a theoretical point of view, it has promise of taking therapy to the next level-that is, addressing issues related to eradication of the disease, of the virus, at least, said Wender, the Francis W. Bergstrom Professor.

Wender and his co-workers Jung-Min Kee and Jeff Warrington have developed a way to synthesize prostratin and DPP, two compounds that occur naturally in plants, in the laboratory. Prostratin, found in the Mamala plant (Homalanthus nutans) that grows in the Samoan rainforest, has shown promise in previous studies as an activator of dormant HIV. DPP, a molecular relative of prostratin found in resin spurge (Euphorbia resinifera), which grows in arid regions, also has shown potential.

Research has been hampered, though, because the compounds are difficult to obtain, particularly in the quantities needed for practical lab work on their mode of action and therapeutic potential. The yield from both plants is low and highly variable; the availability of the plants is limited; and isolating the compound is difficult. Heavy harvesting of the wild plants, especially in Samoa, also could cause ecological damage.

But synthetic prostratin and DPP, which now can be readily made in the lab, changes that equation.

We have now minimized, if not eliminated, the issue of availability of prostratin and DPP, Wender said. But equally, if not more importantly, we have opened access to other compounds that might be similar in structure but superior in function.

Previous work done in mice by researchers at the University of California-Los Angeles indicates that prostratin, used in combination with interleukin-7, an immune system stimulator made in bone marrow, managed to flush out and eliminate approximately 80 percent of the dormant virus. But with HIV, 80-percent efficiency is not enough. Anything less than 100 percent means the virus is still lurking in the T-cells and will spring back to action as soon as an opportunity presents itself.

Nature has produced these compounds for various reasons in the plants from which they're derived, but certainly not to treat human maladies, Wender said. They're not optimized for human therapy.

But with synthetic prostratin and DPP available, researchers can take the basic compounds and tinker with the structure and related function. We could find out how to improve them by reverse engineering: figuring out what is important and what isn't important, Wender said. We could begin to design and synthesize molecules that would never be found in nature but might actually be therapeutically more beneficial than what has been found thus far.

In the Science paper, Wender and his team detail how both compounds can be synthesized, but also show the initial phase of designing and making new derivative compounds.

Although prostratin has long been used by traditional Samoan healers without their patients experiencing acute side effects, it is possible that undesirable effects could show up in an immune-impaired patient taking prostratin or DPP. But Wender noted that engineering the compounds in a lab would permit scientists to circumvent these problems. Usually these kinds of side effects are a result of a drug hitting multiple targets. So it hits one target, which is beneficial, but then it hits some other target, too, he said. But by modifying the structures, you could select for the beneficial activity over the non-beneficial activity.

It's a little bit like draw poker, Wender said. The important point is that we're not forced to use the hand we get. We'll get a hand and we'll return a few cards if we don't like it, because we can keep on tuning this until we get it right, so that a royal flush, hopefully, can be realized.

Wender's team developed their method of synthesizing prostratin and DPP by using a renewable resource, croton oil, made from the seeds of a small tree (Croton tiglium) cultivated in Asia. They derived phorbol from the croton oil and then converted it into the structure of prostratin.

The conversion process required some engineering finesse; they had to overcome a hurdle when, by removing an oxygen atom, they triggered a series of anticipated but seemingly undesired changes.

To the credit of my coworkers, Jung-Min Kee and Jeff Warrington, they employed a strategy that sometimes is missed, Wender said. Rather than fighting the flow, they went with it. They found a way to redirect the chemical complications into a solution to the problem that proved even better than the route they had initially sought to follow.

Eventually they produced a shorter, more economical way of connecting our starting material, phorbol, to our target, prostratin, Wender said. The process Kee and Warrington came up with requires only five steps, which is of tremendous importance in making it economically feasible. As Wender pointed out, steps cost money and human time.

Wender emphasized that the work of his team is the most recent chapter in efforts of a truly global community, starting with the Samoan healers, who willingly shared their knowledge with Paul Cox, an ethnobotanist who saw them prescribing a tea made from Mamala bark for patients with hepatitis-like symptoms. Cox, in turn, sent samples to the National Institutes of Health, in hopes that the bark might have antiviral properties useful in fighting some cancers. Researchers at NIH then analyzed the bark and isolated prostratin.

Prostratin belongs to a class of compounds called tiglianes, many of which promote tumor growth, so it had no initially perceived use in fighting cancer. But NIH researchers found that prostratin was not a tumor promoter and checked to see if perhaps it could help combat HIV, which is when its remarkable ability to flush out the dormant virus was discovered. Significantly, prostratin has also been found to block uptake of the purged virus, offering yet another potentially therapeutic benefit.

The whole effort is a testimonial to a global community working to deal with what I think is a global, and top priority, problem, Wender said.

UT-ORNL and UCSD researchers find promise in HIV 'switch'

Sun, 16 Mar 2008 04:00:00 PST

( from http://www.rxpgnews.com ) KNOXVILLE -- If the battle against HIV, the virus that causes AIDS, is a chess match, then new research published today gives new insight into one of the virus' most important moves.

The findings, by University of Tennessee, Knoxville, and Oak Ridge National Laboratory researchers Michael Simpson and Roy Dar, with colleague Leor Weinberger who led the research at the University of California, San Diego, reveal new information about how a critical genetic switch in the virus operates. They are published as a letter in the upcoming issue of Nature Genetics.

When HIV infects an immune cell, it can enter one of two states: activation, where the virus replicates and then destroys the host cell; and latency, where the viral genetic material continues to exist in the cell, but there is no production of additional virus.

While latency is a ticking time bomb, said Simpson, a possible therapeutic goal could be to stably maintain latency indefinitely.

Previous work by Weinberger found that the genetic circuit that controls whether HIV chooses to go active or latent is not a simple on-off switch, but instead is controlled by a type of genetic pulse -- when the pulse lasts a certain amount of time, the switch will activate replication of the virus.

Now the three researchers have demonstrated that it is possible to manipulate the lengths of the pulses in a way that would favor the selection of latency.

This is vital, said Simpson, because the switch is a definitive factor in whether the virus will become active. If the pulse does not last long enough, he said, the virus cannot become active.

This is an early step, but an encouraging one, said Simpson. HIV has evolved a very effective infection strategy, so the name of the game is understanding how that strategy operates in order to find a way to defeat it.

A challenge of the work, according to Simpson, is that the process involved in how the switch operates cannot be directly observed. Instead, the researchers had to rely on an analysis of the noise created within the cell by the process to determine how it worked.

Simpson and Dar conducted their work in the Center for Nanophase Materials Science at ORNL, a recently opened facility that Simpson says has made this type of analysis possible.

Moving forward, the next step in the research is to determine whether it is viable to attempt to control the switch as part of therapeutic treatment for HIV. The researchers also hope to apply the techniques they used to understanding the operation of other types of human cells.

Scientists say tropics are next emerging disease hotspot

Thu, 13 Mar 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists from four well-known institutions say the next major disease like HIV/AIDS or SARS could occur in any of a number of developing countries concentrated along the equator. They encourage increased surveillance to prevent the spread of a potential outbreak.

Using global databases and sophisticated computer models to analyze patterns of emerging diseases, the researchers -- from the Consortium for Conservation Medicine (CCM) at Wildlife Trust, N.Y., the Institute of Zoology, London, U.K., Columbia University, N.Y., and the University of Georgia, Athens, Ga. -- are able for the first time to plot, map and predict where the next pandemic might occur.

Funded through a Human and Social Dynamics Exploratory Research award from the National Science Foundation (NSF), Arlington, Va., the research represents a major breakthrough in understanding where and why pandemic diseases emerge and provides a key tool for preventing them in the future.

This is an important area of research, said Rita Teutonico, advisor for integrative activities in NSF's Directorate for Social, Behavioral and Economic Sciences. After years of debate, the scientific community is now able to offer a convincing, predictive tool to help policy professionals and resource managers better allocate global resources in the fight against emerging diseases.

By analyzing global patterns in human population density, population changes, latitude, rainfall and wildlife biodiversity in correlation with patterns of emerging diseases, the researchers were able to show for the first time definitive proof that the number of emerging diseases is increasing.

They cite zoonoses -- diseases that originate in animals -- as the primary problem and conclude these are the most current and important threat to humans. The research shows that the key threat to public health is where human population growth and wildlife diversity clash, said Peter Daszak, executive director of the Consortium for Conservation Medicine at Wildlife Trust.

The scientists analyzed 335 incidents of previous disease emergence and were able to identify the regions where future diseases were most likely to occur. They plotted the results on a global, Emerging Disease Hotspots map.

Our hotspots map shows that the next new important zoonotic disease is likely to originate in the Tropics, a region rich in wildlife species and under increasing pressure from people, Daszak said.

This is the first time researchers are able to provide a scientific prediction of where the next major disease like HIV or SARS could emerge. During the last three decades, researchers have spent billions of research dollars to deal with the seemingly random emergence of dozens of pandemics. None of their efforts to understand patterns of emergence were successful.

This new research, published in the February 21 edition of the leading scientific journal Nature, successfully examined over 50 years of disease emergence patterns using a specially designed computer database to pinpoint regions of the world that need more monitoring.

This is a seminal moment in how we study emerging diseases, said Professor John Gittleman, dean in the University of Georgia's Odum School of Ecology, who developed the team's approach to analyzing global databases.Our study has shown that bringing ecological sciences and public health together can advance the field in a dramatic way.

But in light of this new information, the researchers note that additional resources need to be properly directed to safeguard public health.

Most of our resources are focused on the richer countries in the North that can afford surveillance, said Daszak. This is basically a misallocation of global health funding, and our priority should be to set up 'smart surveillance' measures in the hotspots, most of which are in developing countries.

If we continue to ignore this important preventative measure, then human populations will continue to be at risk from pandemic diseases, he said.

Novel mathematical model predicts new wave of drug-resistant HIV infections in San Francisco

Sun, 17 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) A mathematical model shows that a new wave of drug-resistant HIV is rising among among men in San Francisco who have sex with men and that this trend will continue over the next few years, according to a new study from the UCLA AIDS Institute.

At the same time, the evolution of drug-resistant HIV may have actually reduced the severity of the city's epidemic, saving many men from becoming infected.

The model and its results were unveiled today by UCLA biomathematics professor Sally Blower, director of the Biomedical Modeling Center at the David Geffen School of Medicine at UCLA, during a session on drug-resistant diseases at the annual American Association for the Advancement of Science conference in Boston.

Our amplification cascade model has been validated by our reconstructions and can now be used to design novel and effective health policies for controlling single-, dual- and triple-class resistant strains of HIV in both resource-rich and resource-constrained countries, said Blower, who is also a member of the UCLA AIDS Institute.

The model enabled the researchers to reconstruct the epidemic's past and predict its future by calculating the evolution of several classes of drug-resistant HIV strains in San Francisco.

The research relied on a novel multi-strain mathematical model called the Amplification Cascade Model to examine the rise between 1987 and 2007 of HIV strains resistant to the three major classes of drugs -- nucleosides (NRTIs), nonnucleosides (NNRTIs) and protease inhibitors (PIs). The model took into account three interacting processes -- transmitted, acquired and amplified resistance -- the last of which refers to amplification of drug-resistant strains in HIV-positive people due to the repeated use of multiple-treatment drug regimens.

The study tracked uninfected individuals; newly infected people in the primary stage of infection; chronically infected individuals who were not yet eligible for treatment; chronically infected people who remained untreated, though eligible for it; and patients under treatment.

Researchers found complex waves of rising and falling single-, dual- and triple-class drug-resistant HIV strains over 20 years, with more complex patterns continuing to evolve.

The model predicts that resistance to NRTIs will decline substantially and PI resistance will fall slightly through 2012, and that resistance to NNRTIs will rise over the next five years and then begin falling.

Although strains with dual- and triple-class resistance will be transmitted, they will be far less potent than wild-type HIV strains -- those strains that have not developed drug-resistant mutations and remain sensitive to all classes of drugs.

Most surprising of all, the evolution of drug-resistant HIV strains has substantially reduced the severity of the San Francisco AIDS epidemic because the strains that have emerged have become less infectious than the wild-type strains.

Enzyme structure reveals new drug targets for cancer and other diseases

Thu, 14 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) If the genome is the parts list of the human cell, certain proteins are the production managers, activating and deactivating genes as needed. Scientists funded by the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health, now have a clearer understanding of how a key protein controls gene activity and how mutations in the protein may cause disease. The work could provide new avenues to design drugs aimed at cancer, diabetes, HIV, and heart disease.

The research appears in the Feb. 14, 2008, issue of the journal Nature. The lead authors include Philip Cole, M.D., Ph.D., of the Johns Hopkins University School of Medicine in Baltimore, Md., and Ronen Marmorstein, Ph.D., of the Wistar Institute in Philadelphia, Pa.

The investigators focused on a protein called p300/CBP that belongs to a family of enzymes known as histone acetyltransferases, or HATs. These enzymes activate genes by attaching chemicals called acetyl groups to histones, the spool-like proteins that hold DNA in a tightly wound form.

Mutations in p300/CBP are linked to a variety of cancers, including those of the colon, breast, pancreas, and prostate. Researchers believe that a substance that selectively inhibits p300/CBP might be the basis for an anticancer agent.

Nearly 10 years ago, Cole and his coworkers designed a p300/CBP inhibitor. But the inhibitor is not active in the human body, so it has been used exclusively as a research tool.

In the new study, the investigators combined X-ray crystallography with detailed enzymology to understand how p300/CBP works.

Their three-dimensional crystal structure provides an image of how a key part of p300/CBP binds to the inhibitor. Their studies of numerous mutant versions of the enzyme reveal which amino acids in p300/CBP are essential for its activity.

The work has a number of clinical implications. Understanding the structure and behavior of p300/CBP will help scientists design a p300/CBP inhibitor that might function in human cells as an anticancer drug.

Proper functioning of p300/CBP is critical for insulin regulation and the health of heart cells. As a result, compounds that can regulate p300/CBP activity might be useful in the treatment of diabetes and heart disease.

In addition, HAT activity is necessary for the multiplication of HIV, leading at least one scientific group to suggest that targeting HATs or similar enzymes might be an new way to thwart the virus.

Finally, the article also shows that some p300/CBP mutations previously linked to certain cancers lie right where p300/CBP contacts the inhibitor. Studying how these mutations alter the enzyme's function should shed light on why the mutations can lead to disease.

This work illustrates how enzymology and structural biology can combine to yield both fundamental and practical insights about an important biomedical problem. The studies provide a new framework for understanding p300/CBP in health and disease, said Jeremy M. Berg, NIGMS Director.

HIV persists in the gut despite long-term HIV therapy

Wed, 13 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Even with effective anti-HIV therapies, doctors still have not been able to eradicate the virus from infected individuals who are receiving such treatments, largely because of the persistence of HIV in hideouts known as viral reservoirs. One important reservoir is the gut, where HIV causes much of its damage due to the large number of HIV target cells that reside there. These cells, known as CD4+ T cells, are largely contained in lymph nodes and patches of lymphocytes that collectively are called gut-associated lymphoid tissue, or GALT.

Because of the importance of the gut to HIV disease, scientists hoped that long-term treatment with antiretroviral drugs could eradicate HIV from the GALT. A new NIAID study, published online by The Journal of Infectious Diseases, has found that this goal seems unlikely with current antiretroviral drugs.

Tae-Wook Chun, Ph.D., of the NIAID Laboratory of Immunoregulation (LIR), Anthony S. Fauci, M.D., LIR chief and NIAID director, and their colleagues intensively studied eight patients receiving effective antiretroviral therapy for up to 9.9 years. In each of these of these individuals, therapy had consistently kept their blood levels of HIV at undetectable levels. Sensitive tests, however, detected the persistence of HIV as well as lowered CD4+ T cell levels in the GALT that did not completely rebound in response to therapy. Levels of virus were higher in the GALT than in immune cells in the blood, where HIV also was consistently found. In addition, the scientists found evidence of cross infection between the GALT and the lymphocytes in the blood, suggesting that one reason the virus persists in the blood is because of ongoing cycles of replication in the GALT. The authors conclude that any possibility of further lowering or eliminating viral reservoirs likely will require more powerful drug regimens to stop the low levels of ongoing viral replication originating in the GALT. The development of such regimens is an important goal of NIAID-supported research.

A second study from the Fauci laboratory, conducted by Susan Moir, Ph.D., and her colleagues and also published online by The Journal of Infectious Diseases provides additional insights into the effects of antiretroviral therapy on the HIV disease process.

In most HIV-infected individuals, the virus replicates at high levels and CD4+ T-cell numbers decline. These two factors also strongly affect B cells, the cells of the immune system that make antibodies and help protect against infection. Dr. Moir and her colleagues demonstrated that prior to treatment with antiretroviral therapy, B-cell numbers in the blood of HIV-infected individuals who have been infected for several years are low, and the B cells also include several dysfunctional subsets. After one year of effective treatment with antiretroviral therapy, B-cell numbers returned to normal, and several of the dysfunctional subsets also normalized. However, those B-cells that provide long-term protection against infection--so-called memory B cells--did not return to normal levels. Dr. Moir notes that these findings strengthen the notion that while antiretroviral therapy improves many aspects of immune function in HIV-infected individuals, important deficiencies remain, especially in individuals who wait several years before initiating therapy. More studies are needed to determine whether early initiation of antiretroviral therapy helps restore the immune system more completely.

HIV drugs, Abacavir and Didanosine increase the risk of heart attack

Fri, 08 Feb 2008 04:25:00 PST

( from http://www.rxpgnews.com ) A study to assess the adverse effects of anti-retroviral drugs
shows that two widely-used HIV drugs are associated with
an increased risk of heart attack/the formation of blood clots in
the heart. With the use of Didanosine, the risk of developing a
heart attack increases by 49%, with Abacavir; the increased risk
is 90%. The effect is most pronounced in patients with a high
underlying cardiovascular risk. The research findings also show
that the adverse effect is reversible, if patients discontinue use
of these particular drugs.

The scientists who conducted the study recommend that patients
on Abacavir or Didanosine should evaluate their underlying
cardiovascular risk with their doctor and discuss whether any
changes to their drug regime are warranted. The scientists
strongly urge HIV patients not to stop taking Abacavir or
Didanosine, before they have consulted their doctor.

Since the study began in 1999, D:A:D (the Data Collection of Adverse
effects of Anti-HIV Drugs Study) has examined the side-effects of
anti-retroviral drugs, including a possible increase in the risk of heart
attack. Recent analysis has focused on a class of drugs, not previously
examined, known as the nucleoside analogues, which inhibit the HIV
virus by preventing it from multiplying. This class of drugs includes Stavudine, Zidovudine, Lamivudine, Abacavir and Didanosine. Only the last two drugs in the analysis were shown to have an adverse effect with respect to heart disease.

The side-effects associated with Didanosine and Abacavir are, naturally, most significant for HIV-infected patients who already have a high underlying cardiovascular risk. The drug effect increases an individual persons underlying risk by a factor
of 1.9 for a person on Abacavir, and 1.49 for a person on Didanosine. For a person with a low underlying risk, this increase in risk is still negligible, but for someone with a high
underlying risk, this could have serious consequences. The study shows, however, that the risk of heart attack is removed once patients stop taking the drugs. This seems to be the case, regardless of
how long these drugs have been used by patients.

The D:A:D study involves over 33,000 patients from Europe, Australia and Asia. The study evaluates the incidence of heart attack among HIV-infected patients undergoing anti-retroviral treatment, and thereby enables scientists to determine whether side-effects of the anti-retroviral drugs, including cardiovascular disease, are increased in the long-term.

Breastfeeding now safer for infants of HIV-infected mothers

Tue, 05 Feb 2008 20:30:00 PST

( from http://www.rxpgnews.com ) An antiretroviral drug already in widespread use in the developing world to prevent the transmission of HIV from infected mothers to their newborns during childbirth has also been found to substantially cut the risk of subsequent HIV transmission during breast-feeding.

In a study presented Feb. 4 at the 2008 Conference on Retroviruses and Opportunistic Infections in Boston, an international team of AIDS experts reports that nevirapine given once daily to breast-feeding infants from 8 to 42 days old decreased by almost half the rate of HIV transmission via breast-feeding at 6 weeks of age. The decrease occurred in comparison to a single dose of nevirapine given to infants at birth, the current standard of care. At 6 months of age, the risk of postnatal HIV infection or death in infants who received the six-week regimen was almost one-third less than the risk for infants given only a single dose. The study was led by three teams of investigators at The Johns Hopkins University in collaboration with investigators in Ethiopia, India and Uganda.

Breast-feeding remains a leading route of HIV transmission in the developing world. The United Nations World Health Organization estimates that approximately 150,000 infants are infected through breast-feeding each year. In the United States each year, fewer than 150 newborns are infected with HIV at birth, mostly to mothers who did not know they were HIV positive.

Eltrombopag effective for hepatitis C patients with low blood-platelet counts

Fri, 28 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 28, 2007) -- For patients with hepatitis C, having a low blood platelet count is a frequent complication associated with advanced disease. This problem is compounded by the fact that standard antiviral treatment for the disease can further reduce platelet numbers to dangerously low levels, effectively denying these patients the treatment they urgently need. Now, research published in the New England Journal of Medicine finds that a new drug, eltrombopag, appears to significantly boost platelet counts, opening the door to effective treatment.

In this study, eltrombopag increased platelet counts in a dose-dependent manner, allowing more patients to complete the first 12 weeks of antiviral therapy -- an important treatment goal, says Dr. Samuel Sigal, who led the study at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City -- one of 22 study sites.

Dr. Sigal is assistant professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medical College and assistant attending hepatologist in the Center for Liver Diseases and Transplantation at NewYork-Presbyterian/Weill Cornell.

The Phase 2 placebo-controlled study followed 74 patients with low platelet counts and cirrhosis of the liver due to hepatitis C virus (HCV) infection. Seventy-four percent of those randomized to take the lowest dose (30 milligrams daily) saw their platelet counts go up significantly, while 79 percent and 95 percent of the participants saw increases with the higher doses (50 or 75 milligrams daily, respectively). And, 12 weeks of antiviral therapy were completed by 36, 53 and 65 percent of patients at the three dose levels -- with increased numbers matched to the size of the dose. Underlining the trend, less than a quarter of patients receiving placebo completed their therapy.

The study identified side effects -- including headaches, dry mouth, abdominal pain and nausea. None were serious enough to discontinue the therapy.

It's estimated that 4 million people in the U.S. and 170 million worldwide carry the hepatitis C virus. HCV is transmitted primarily by blood and blood products. The majority of infected individuals have either received blood transfusions prior to 1990 (when screening of the blood supply for HCV was implemented) or have used intravenous drugs. More rarely, it can also be transmitted through sexual intercourse and perinatally (mother to baby).

The virus causes inflammation and scarring in the liver, and while it is curable in about half of those who have it, it can lead to significant liver damage, liver cancer and death in others. HCV infection is a common cause of cirrhosis and the most common reason for a liver transplant.

With other eltrombopag findings, NewYork-Presbyterian/Weill Cornell's Dr. James Bussel led research, also reported in the New England Journal of Medicine, finding the platelet growth factor successfully increased platelet counts and decreased bleeding in patients with Immune Thrombocytopenic Purpura (ITP), an autoimmune disease that dramatically reduces the number of platelets in their blood. (Dr. Bussel is an Advisory Board Member for GlaxoSmithKline; has received research grant support, lecture fees, and consulting fees from GlaxoSmithKline; and reports equity ownership in the company.)

The current study was sponsored by GlaxoSmithKline, which is developing eltrombopag. Eltrombopag (marketed as Promacta in the U.S. and Revolade in Europe) is an investigational oral, non-peptide platelet growth factor that induces the proliferation and differentiation of cells to produce platelets. While other drugs that restore normal platelet functions are infusions or injections, eltrombopag is a once-a-day pill.

2 genes are important key to regulating immune response

Fri, 28 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 28, 2007) -- A research team at Weill Cornell Medical College in New York City has identified two genes that may be crucial to the production of an immune system cytokine called interleukin-10 (IL-10).

The discovery fills in an important missing link in a biochemical pathway that's long been tied to disorders ranging from lupus and Type 1 diabetes, to cancer and AIDS.

IL-10 production has to be kept in a delicate balance for health, explains study senior researcher Dr. Xiaojing Ma, Professor of Immunology and Microbiology in the Departments of Microbiology and Immunology and Pediatrics at Weill Cornell. Too much IL-10 can leave the body more vulnerable to killers such as viruses and cancer, and to certain antibody-driven autoimmune diseases such as lupus, while too little can lead to run-away inflammatory pathology. Therefore, a better understanding of IL-10 regulation moves us closer to understanding these illnesses and -- potentially -- how to better treat them, he says.

The findings are reported in this month's issue of Immunity (vol. 27).

Dr. Jianguo Liu, of Weill Cornell, and Dr. Elaine Y. Chung, formerly of Weill Cornell and now a post-doc at the University of Pennsylvania, were co-lead researchers on the study.

Every second, millions of the body's cells undergo naturally programmed cell death -- a process called apoptosis. In healthy individuals, these dying or dead cells are spotted and then quickly ingested and removed by immune system scavenger cells such as macrophages.

However, to prevent this type of clean-up from triggering a wider immune response, macrophages express the IL-10 cytokine in the presence of apoptotic cells.

IL-10 suppresses the activity of immune system T-cells that might otherwise run amuck, Dr. Ma explains.

That can be a good thing, of course, he says. But on the other hand, when immune system T-cell activity is weakened too much, that can help encourage AIDS in those infected with HIV. Also, excessive T-cell suppression can keep the immune system from destroying rogue cancer cells in people battling malignancy.

All of this means that anything that we can learn about IL-10 production -- and related T-cell suppression -- is a boon to medical research, Dr. Ma explains.

Prior studies had already shown that CD36 -- a protein receptor lying on the surface of the macrophage -- was important for the recognition of apoptotic cells by macrophages. In this work, the researchers observed that CD36 also helped to trigger IL-10 production whenever apoptotic cells were around.

The team then asked a deeper question: What signals lead to IL-10 production from CD36 present at the cell surface

To find out, the Weill Cornell group first exposed macrophages to apoptotic (dying) cells. They then used sensitive assays to look for key biochemical changes occurring downstream of CD36 activation.

We found proteins in the cell nucleus that were binding to a site we knew was critical for the production of IL-10 as macrophages encountered apoptotic cells, Dr. Ma says. In subsequent biochemical experiments, the team identified the two genes responsible for the transcription (gene-directed production) of these proteins.

These genes -- pre-B transcription factor 1(Pbx-1) and Pbx-regulating protein 1 (Prep-1) -- are best known to scientists as partners for their role in embryonic development and several forms of leukemia, with Pbx playing a major part in hematopoeisis, the production of new and myriad blood cell types.

In that sense, their presence as immune system transcription factors came as a big surprise to us, Dr. Ma says. In fact, we still haven't figured out exactly how Pbx-1 and Prep-1 are involved in regulating IL-10 transcription. I really hope this study opens up new avenues for immunologists to find out whether there's a brand new biochemical pathway to be discovered.

The findings could also reveal exciting new information as to how aberrant IL-10 expression contributes to disease.

Because IL-10 expression (and related T-cell suppression) are so important to the etiology of so many illnesses, discoveries like ours could point to molecular pathways that may become important new targets for drug discovery going forward, Dr. Ma explains. It's these types of breakthroughs in the lab that -- step by step -- will end up bringing real hope to patients down the line.

Dr. Lewis Drusin receives American College of Physicians James D. Bruce Memorial Award

Wed, 19 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Dec. 19, 2007) -- In recognition of his distinguished contributions in preventive medicine, epidemiologist Dr. Lewis Drusin of NewYork-Presbyterian Hospital/Weill Cornell Medical Center has been selected by the American College of Physicians to receive the prestigious James D. Bruce Memorial Award, one of 17 awards in internal medicine for 2008.

The convocation ceremony will take place on May 15, 2008, at the annual meeting of the American College of Physicians in Washington, D.C.

Past recipients include such notables as Nobel Prize winner Dr. Jonas Salk (polio vaccine), Dr. Donald Henderson (smallpox) and NewYork-Presbyterian/Weill Cornell's Dr. Walsh McDermott, who served as a mentor to Dr. Drusin.

Dr. Drusin is professor of clinical medicine and professor of clinical public health at Weill Cornell Medical College, and attending physician at NewYork-Presbyterian/Weill Cornell, where he was formerly director of the Division of Epidemiology.

We want to extend our congratulations to Dr. Drusin, whose career-long contributions to preventive medicine make him very deserving of this special honor, say Dr. Antonio M. Gotto, Jr., the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College, and Dr. Herbert Pardes, president and CEO of NewYork-Presbyterian Hospital.

Dr. Drusin has made outstanding contributions to the prevention and study of nosocomial infections and sexually transmitted diseases, publishing more than 50 papers and book chapters. At Weill Cornell, he directs a program placing Public Health and Community Medicine clerkship students in field locations, and has helped establish an endowment that offers international rotations to medical students. He served as president of the American Venereal Disease Association (now the American STD Association), and he has held prominent roles in many international scientific congresses and study groups relating to sexually transmitted diseases. Since 1995, he has served as the main representative of the International Union Against Sexually Transmitted Infections to the Economic and Social Council of the United Nations. He is a fellow of the American College of Physicians, a fellow of the Royal College of Physicians of London and one of only two American honorary life members of the British Association for Sexual Health and HIV.

He earned his undergraduate degree at Union College (Schenectady, N.Y.) and received his medical degree from Cornell University Medical College (now Weill Cornell Medical College). Dr. Drusin also holds an M.P.H. from the Columbia University School of Public Health.

I am deeply honored to be considered among such esteemed company, says Dr. Drusin. It is exiting when you make your career choices according to what's fun to do, and then you find out later that other people have appreciated what you've done.

HIV's path out of Africa: Haiti, the US then the world

Mon, 29 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com )

The AIDS virus entered the United States via Haiti, probably arriving in just one person in about 1969, earlier than previously believed, according to new research.

After the virus, HIV-1, entered the U.S., it flourished and spread worldwide.

Our results show that the strain of virus that spawned the U.S. AIDS epidemic probably arrived in or around 1969. That is earlier than a lot of people had imagined, said senior author Michael Worobey.

The research is the first to definitively pinpoint when and from where HIV-1 entered the United States and shows that most HIV/AIDS viruses in the U.S. descended from a single common ancestor. The actual ancestral HIV entered the U.S. long before the storied Patient Zero, Worobey said.

Haiti was the stepping stone the virus took when it left central Africa and started its sweep around the world, said Worobey, an assistant professor of ecology and evolutionary biology at The University of Arizona in Tucson. Once the virus got to the U.S., then it just moved explosively around the world.

The strain that migrated to the U.S. in 1969, HIV-1 group M subtype B, is the first human immunodeficiency virus discovered. It is the dominant strain of the AIDS virus in most countries outside sub-Saharan Africa. Almost all the viruses in those countries descended from the one that emerged from Haiti, he said.

Worobey and his colleagues figured out when HIV reached the U.S. by conducting genetic analyses of archived blood samples from early AIDS patients.

Learning more about the genetic make-up of the various strains of HIV could help vaccine development, Worobey said.

The scientists' research paper, The emergence of HIV/AIDS in the Americas and beyond, is scheduled for publication in the online Early Online edition of the Proceedings of the National Academy of Sciences the week of October 29.

Worobey's co-authors are M. Thomas P. Gilbert of the University of Copenhagen in Denmark; Andrew Rambaut of the University of Edinburgh in Scotland; Gabriela Wlasiuk of the UA; Thomas J. Spira of the Centers for Disease Control and Prevention in Atlanta, Ga.; and Arthur E. Pitchenik of the University of Miami in Fla. The National Institutes of Health, the David and Lucile Packard Foundation and a University Research Fellowship from The Royal Society funded the research.

Figuring out which path HIV/AIDS took as it began its world travels and when it moved from one country to another has long been a topic of scientific investigation and debate.

Worobey and his colleagues tackled the problem by using archived blood samples from AIDS patients to construct genetic family trees for HIV.

The team analyzed blood from five of the first AIDS patients identified in the U.S., all of whom were recent immigrants from Haiti. The team also analyzed genetic sequences from another 117 AIDS patients from around the world who were infected with subtype B, the virus strain that has spread most widely.

Once all the sequences were assembled, the researchers loaded the data into a computer and used Bayesian statistics to investigate all the family trees that were consistent with the genetic data. The researchers then evaluated all possible HIV family trees to determine how probable a particular family tree is.

For the hypothesis that, from Africa, HIV went to the U.S. first, the probability is 0.003 percent -- virtually nil.

For the hypothesis that HIV went from Africa first to Haiti and then on to the U.S., the probability is 99.8 percent, almost 100 percent.

The analysis also shows that the ancestry of most viruses in the U.S. can be traced back to one common ancestor -- the virus that came from Haiti in about 1969.

Before this study, that had not been nailed down, Worobey said.

The research also reveals that Haiti has a much larger genetic diversity of subtype B than does the U.S.

The U.S., Australia, Europe plus many countries have just a subset of the subtype B diversity you see in Haiti, Worobey said.

The virus moved from Africa to Haiti in about 1966, he said. Haiti has more diversity of HIV than does the U.S. and other countries because the virus has been there longer and had more time to mutate.

The finding helps explain the early observations of a high prevalence of AIDS in Haiti, Worobey said. The virus had simply been there longer.

The main challenge of developing a vaccine against HIV is its tremendous genetic diversity, he said.

Knowing the gamut of diversity within subtype B could be important for effectively developing and testing vaccines that will work in Haiti, Worobey said.

Worobey's next step is following the trail of HIV even further back in time using older archival samples.

HIV patients sicker when seeking care than in the past

Thu, 25 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) It was hoped that as HIV treatment improved and as HIV-related public health initiatives encouraged people to be tested for the disease and seek care, that HIV-infected patients would seek care quickly. Unfortunately, a new study indicates that patients are actually sicker when they begin therapy. The study is published in the November 15 issue of Clinical Infectious Diseases, currently available online.

The study, carried out in Baltimore, MD, from 1990 through 2006, shows that HIV patients beginning HIV therapy have trended toward increasing levels of immunocompromise. This is probably an indicator that people are getting tested for HIV later after they�ve contracted the disease than in the past. Also, people in several key demographic groups are not any quicker now to seek care than they were in the past and some are even taking longer.

HIV is a disease that is most effectively treated if caught early in the course of the illness. Early treatment also helps to limit the spread of the virus from one person to another. For these reasons, HIV services in the United States have evolved over time to encourage people to be tested for HIV and seek treatment if infected.

The researchers, Jeanne Keruly, MS and Richard Moore, MD, of Johns Hopkins University School of Medicine in Baltimore, analyzed data from over 3,300 patients seeking HIV care from the Johns Hopkins HIV service. The data were examined both as a whole and as demographic subsets including gender, race, injecting drug use, men who have sex with men, and heterosexuals. They looked at the amount of time between a patient�s diagnosis of HIV and the time when that person first sought care; and they looked at the patient�s immune status at the time of first care. Ideally, they would have found trends that showed a decrease in the time between diagnosis and treatment and an increase in the immune status.

During the years analyzed, men�and in particular white men and men who have sex with men�did have a trend towards seeking care more quickly after receiving an initial diagnosis of HIV. For all men, the average length between diagnosis and presentation for care was 270 days at the beginning of the study, falling to 183 days by the end.

Women�s times to seek treatment, on the other hand, stayed fairly constant. And, unfortunately, injection drug users had a dramatic increase in the time until treatment, from an average of 378 days at the beginning of the study to 630 days at the conclusion.

People in all but one of the demographic categories had a trend of increasing immunocompromise, an indicator of disease development. The level of immunocompromise was such that the person was at increased risk for a poorer clinical outcome from antiretroviral therapy than if they had presented earlier for care. Over time, patients were increasingly likely to present with AIDS or HIV symptoms. The exception was in the men who have sex with men category.

In light of what appears to have been a poor response to efforts to more rapidly diagnose and treat HIV patients in Maryland, the authors call for new strategies to provide earlier HIV testing and referral into care.

Smoked cannabis proven effective in treating neuropathic pain

Wed, 24 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.

In the placebo controlled study of 15 subjects, a low dose of cannabis showed no effect, a medium dose provided moderate pain relief, and a high dose increased the pain response. The results suggest a therapeutic window for cannabis analgesia, according to lead researcher Mark Wallace, M.D., professor of anesthesiology at UCSD School of Medicine and Program Director for the UCSD Center for Pain Medicine.

The paper, to be published in the November issue of the journal Anesthesiology, is the second published study out of the CMCR. Headquartered at UCSD, the CMCR is collaboration between UCSD and UC San Francisco that was funded by a state-funded initiative in 1999 to rigorously study the safety and efficacy of medicinal cannabis in treating diseases.

The study used capsaicin, an alkaloid derived from hot chili peppers that is an irritant to the skin, to mimic the type of neuropathic pain experienced by patients with HIV/AIDS, diabetes or shingles � brief, intense pain following by a longer-lasting secondary pain. The subjects were healthy volunteers who inhaled either medical cannabis or a placebo after pain was induced. The marijuana cigarettes were formulated under NIH supervision to contain either zero, two, four or eight percent delta-9-tetrahydrocannabinol (THC.)

�Subjects reported a decrease in pain at the medium dose, and there was also a significant correlation between plasma levels of THC, the active ingredient in cannabis, and decreased pain,� said Igor Grant, M.D., F.R.C.P.(C), professor and Executive Vice-Chair of the Department of Psychiatry, the director of the CMCR. �Interestingly, the analgesic effect wasn�t immediate; it took about 45 minutes for the cannabis to have an impact on the pain,� he said.

The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR�s first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain�twice the rate experienced by patients receiving a placebo.

�This study helps to build a case that cannabis does have therapeutic value at a medium-dose level,� said Grant. �It also suggests that higher doses aren�t necessarily better in certain situations � something also observed with other medications, such as antidepressants.�

The researchers stated that more and larger studies need to be conducted to measure the efficacy of cannabis, noting that medical marijuana could play an important role in treating patients who don�t respond well to the usual pain relievers or can�t tolerate drugs such as ibuprofen or opioids used for severe pain.

�The results of this study might help guide others doing clinical research into pain management,� said Wallace.

Fight against HIV needs local scientists, say researchers

Mon, 22 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists from developing countries are vitally important in the fight against HIV and they must be given the proper resources to conduct their work, according to a new commentary published today in the journal Nature Immunology.

Researchers from Imperial College London, who are evaluating multiple candidate vaccines designed to prevent HIV, argue that Western governments and funding agencies must commit to sharing technology and expertise with those in the developing world on a long-term basis.

The researchers have been working with local scientists in Uganda and other sites in the developing world to enable large-scale international trials of potential vaccines against HIV. They argue their work shows that it is both feasible and desirable to carry out high-quality trials in developing countries, but that more state-of-the-art laboratories are needed in the developing world to support such trials and enable the roll-out of antiretroviral drugs.

The authors write that people in countries like Uganda wish to take ownership of, or at the very least be equal partners in, efforts to develop treatments for HIV to benefit their population.

�Old fashioned �parachute science� � where scientists from the developed world flew in, bled a few patients, and immediately returned to their country of origin with their samples, are no longer required or acceptable. In-house development and research is an effective and efficient way forward,� said Professor Frances Gotch, one of the commentary�s authors from the Division of Investigative Science at Imperial College.

Uganda is a relative success story in relation to other parts of sub-Saharan Africa in terms of how it has dealt with the spread of HIV, thanks to a National AIDS Control programme, which was established early in the epidemic. Nonetheless, one million people in the country are living with HIV and contributions from the West have been and continue to be crucial in Uganda and elsewhere, say the authors.

Collaborations across sub-Saharan Africa have so far enabled the creation of network of state-of-the-art laboratories, staffed by local scientists and technologists. Cooperation between the Ugandan government and international bodies has enabled the development of research which has led to improved HIV screening and counselling; free mosquito nets and water purification to prevent opportunistic infections; and free testing and treatment for basic infections of danger to those living with AIDS.

�Western governments and funding agencies need to continue to build capacity and train future generations of scientists and doctors on-site in new technologies,� added Professor Gotch. �Countries need resources to maintain and sustain not only the facilities and equipment, but also staff in these countries who are trained and motivated. It is most important to give countries the capacity to train the trainers in their country so that knowledge can be shared and developed there.�

The commentary is part of the Council of Science Editors' global theme issue on poverty and human development, launched today by the National Institutes of Health to coincide with the publication of related research by more than 230 journals worldwide.

Clues to ensuring anti-HIV drugs are taken in Africa

Mon, 22 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. � HIV-infected patients in the African country of Tanzania were more likely to stop taking their medications and to fail treatment if they had to pay for the drugs themselves.

According the results of a new study conducted by Tanzanian physicians and Duke University Medical Center researchers, HIV-infected patients who openly discussed their illness were also more likely to fare better.

�Our findings suggest that efforts to provide free medication to HIV-infected patients and to promote social coping may increase the chances that patients will continue taking their medications and therefore have stronger immune systems and live longer,� said Habib Ramadhani, M.D., physician at the Kilimanjaro Christian Medical Centre and lead author of a paper appearing early online in the journal Clinical Infectious Diseases. Infectious disease specialists from Duke collaborate with the Kilimanjaro medical center physicians at a clinic in Moshi, Tanzania.

The findings of this and other studies in sub-Saharan African countries should help policy makers and physicians figure out how best to direct and manage the increase in the amount of powerful HIV-fighting drugs that are flowing into the continent, the researchers said. This group of drugs, known generally as anti-retroviral therapy, can suppress the levels of virus in the blood to almost non-detectable levels and prolong life.

In order to better understand the barriers that may keep patients in such economically challenged countries from successfully fighting the disease, the researchers studied 150 HIV-infected patients seen at the Moshi clinic, paying particular attention to how well patients were adhering to their medication regimens and how successfully the levels of virus in the blood was responding to the therapy.

About one in six of the patients reported not taking their medications according to schedule, and the patients more likely to have stopped complying were those who had spent a larger proportion of their time on treatment paying for the antiretroviral medicines themselves. These patients typically used their scant resources on other necessities, such as food and shelter, rather than the medicines, researchers said.

They also found that about one in three patients had increases in the level of virus in the blood consistent with treatment failure, and not surprisingly, the patients who were not taking their drugs were more likely to have treatment failure.

�Another quite interesting finding was that being public about their HIV status was associated with suppression of virus,� Ramadhani said. �There still is a substantial stigma associated with HIV in Africa. It is likely that individuals infected with HIV who discussed their disease with friends or family members are likely living in supportive environments that promote adherence.�

The researchers also found that the farther away patients were from the clinic, the less likely they would take their drugs as instructed.

�This study has identified critical factors that affect the success of antiretroviral therapy programs in Africa, and we believe that these findings should be incorporated by policy makers into practice,� said Duke�s John Crump, M.B., Ch.B, who specializes in infectious diseases and international health and is a senior member of the research team. �These drugs, which are known to work, should be free and readily available.

�Structural barriers to care, such as the distance to clinics and especially the burden of patients paying for their medication, must be removed,� Crump continued. �Social coping, including the disclosure of HIV status to people to family and friends leads to better adherence to medication and lower rates of treatment failure.�

According to Michael H., Merson. M.D., director of the Duke Global Health Institute, This study nicely illustrates some of the factors that need to be considered in reducing the health disparities between the haves and have nots throughout the world, and the value of exploring ways to eliminate them through a multidisciplinary lens. Reducing costs, increasing access and lessening stigma are all necessary for providing good AIDS treatment.

Improvement still needed in HIV testing in high-risk groups

Mon, 22 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. � Since 2000, the rates of HIV testing have remained relatively low and constant in the United States, with about one third of Americans ever having had an HIV test, and less than a quarter of the people considered at high risk for contracting the virus that causes AIDS report having been tested in the past year.

The Duke University researchers who conducted an analysis of testing rates argue that while national HIV testing efforts have been expanded to include lower risk populations, there is still untapped potential to increase testing rates among high-risk individuals.

�We found that high-risk groups want to get tested � but their actions don�t match up with their intentions,� said Brian Wells Pence, Ph.D., an infectious diseases epidemiologist at Duke University�s Center for Health Policy and co-author of a study appearing early online in the Archives of Internal Medicine.

The analysis of health surveys of 146,868 Americans showed that those at high risk for HIV, those who were depressed, and those who abused alcohol all demonstrated significant gaps between their intentions to get tested and their actual testing behavior � an observation that did not hold for lower-risk groups.

�Recent policy statements emphasize broadening HIV testing in the general population,� Pence said. �But such efforts should not come at the expense of trying to meet the desire for testing in higher risk groups. The results of our analysis suggest that high-risk groups know they should be tested � so significant potential may still exist to increase testing in such groups by focusing on access. Patients at alcohol and mental health treatment sites, for example, may be receptive to increased testing opportunities.�

People at high risk for contracting AIDS include those who have unprotected sex or who are injection drug abusers.

For their analysis, researchers pooled data collected during six consecutive annual National Health Interview Surveys, beginning in 2000. These detailed federal surveys of more than 35,000 households each year cover a wide variety of topics and are intended to get a �snapshot� of the overall health of the American population. The Duke researchers focused on a particular aspect of the survey results -- the difference between the proportion of individuals reporting an intention to get an HIV test in the coming year and the proportion that had been tested in the past year.

The researchers found that overall, rates of actual testing slightly exceeded rates of planned testing � but the reverse was true among high-risk groups. Specifically, although 27 percent of those at highest risk said they wanted to be tested in the next year, only 11 percent had actually sought out a recent test, Pence said.

�Our analysis suggests that individual and structural barriers keep some individuals, and especially high-risk individuals, from translating their testing intentions into action,� Pence said. �Those who lacked a source of primary health care, for instance, were less likely to act on their intentions to test. The same was true of individuals who reported being depressed or abusing alcohol.�

In a finding that supports the Center for Disease Control and Prevention�s recommendation that HIV testing be included in routine medical care, the Duke team found that about 44 percent of the tests taken during the study period were prompted by encounters with the health care system, such as prenatal care visits or other routine medical appointments. The researchers concluded that the CDC�s efforts to incorporate HIV testing in routine medical care have been successful in making testing more generally available.

The researchers also found that minority women were significantly more likely to get tested than white males.

An estimated 1.1 million Americans are infected with HIV, with about one-quarter of them unaware of their infection. This minority who do not know their status are believed to be responsible for over half of new HIV infections in the United States, making the expansion of HIV testing a top priority for the CDC.

High-risk individuals less likely to follow through on HIV testing plans

Mon, 22 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) One-fourth of individuals at high risk for contracting HIV report planning to be tested for the virus in the next year, but fewer appear to follow through on that intention than individuals who are at lower risk, according to a report in the October 22 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

About 1.1 million U.S. individuals are affected with the HIV virus, and 24 percent to 27 percent do not know they are infected, according to background information in the article. The HIV epidemic is increasingly affecting groups not perceived as being high-risk, including women, the poor and individuals living in rural areas. �Initiatives to increase the rates of HIV testing, particularly among groups not traditionally perceived as being at high risk, have been advanced as a primary strategy in the effort to combat the HIV epidemic,� the authors write.

Jan Ostermann, Ph.D., M.S., of Duke University, Durham, N.C., and colleagues analyzed data from 146,868 adults age 18 to 64 who were interviewed between 2000 and 2005 as part of the National Health Interview Surveys. Participants were asked whether any of a list of HIV risk factors, such as receiving blood clotting factors for hemophilia or using injection drugs, applied to them. They also reported their HIV testing history and whether they planned on being tested in the next year, in addition to how often they drank alcohol, whether they had symptoms of depression and their sociodemographic information, such as age, education and marital status.

Overall, rates of HIV testing remained approximately the same between 2000 and 2005, with 37 percent of participants reporting being tested in their lifetimes and 10 percent within the past year. Females, minorities and individuals who reported greater risks for HIV were more likely to be tested. However, even among those reporting a medium or high risk for HIV, fewer than 25 percent were tested in the previous year.

In addition, �the difference between planned and actual testing was greater for those with greater HIV risk factors,� the authors write. �Indeed, those with a lifetime HIV risk factor, with medium or high self-perceived HIV risk, and with heavier alcohol consumption were all less likely to actually get tested than to report an intention to get tested.� For example, among those who reported a lifetime risk factor for HIV, 16 percent fewer individuals received a voluntary HIV test than reported planning to get tested, compared with a 5.6 percent deficit between planned and actual testing for those with no risk factors.

�These findings suggest that considerable potential exists to increase testing in higher-risk groups if individual and structural barriers can be identified and addressed,� the authors conclude. �Alcohol and mental health treatment sites, for example, may represent a valuable opportunity to increase testing rates for higher-risk populations who exhibit a marked demand for testing. Although compelling arguments have motivated the current focus on general population testing, such efforts should not come at the expense of ensuring access to and utilization of testing by higher-risk groups.�

HIV is spread most by people with medium levels of HIV in blood, says study

Mon, 22 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) People with medium levels of HIV in their blood are likely to contribute most to the spread of the virus, according to new research published today in the journal Proceedings of the National Academy of Sciences.

The study, by researchers from Imperial College London, looked at several groups of HIV-positive people in Europe, the USA and sub-Saharan Africa. It found that those with a high viral load are the most infectious group, but have only limited time to infect others, because they generally progress to AIDS quite quickly.

Viral load - a count of how many viral particles are in a person�s blood � varies hugely between individuals. The higher the viral load, the more infectious a person is but the shorter their life expectancy. As a result, the study found, those with a high viral load do not contribute the most in the long run to the spread of HIV.

Those with a medium viral load are moderately infectious but remain asymptomatic for a period of about six to eight years before progressing to the symptoms of AIDS. This means they can be unaware that they have HIV for a long period of time, during which they can transmit the virus to a number of different sexual partners, and hence contribute most to the epidemic.

Dr D�irdre Hollingsworth, one of the authors of the paper from the Department of Infectious Disease Epidemiology at Imperial College, said: �Just being highly infectious isn�t enough, you have to live long enough to pass the virus on. This long-term view should inform public health policy.�

Despite much recent progress, effective treatment is still not widely available across sub-Saharan Africa, where most infected individuals live. One idea which has been put forward is that treatment should target the most infectious people, with high viral loads, in order to limit transmission. The results of the new study suggest that this would not be an effective plan, as the largest number of new infections is caused by people with medium viral loads.

Those with a medium viral load form the largest, most common group amongst those not receiving treatment. One reason for this could be that the virus has evolved to achieve the optimal balance between infectiousness and virulence, in order to maximise its chances of getting passed on.

Dr William Hanage, another of the authors from the same department at Imperial, commented: �It�s certainly very striking that the viral loads we see most in nature are just right to make sure the virus gets transmitted as much as it can before it kills its host, which is what you would expect from evolution.�

Dr Christophe Fraser, lead author of the study from the Department of Infectious Disease Epidemiology at Imperial College, added: �We now want to see whether the virus has adapted in order to allow it to infect the most people, which seems plausible given the results of our study. This would have serious implications for public health policy, because if it is true then some strategies to prevent transmission could end up making the virus more virulent by accident. While it is too early to sound the alarm, more research to prove or disprove this theory is urgently needed. That is what we are focusing on now.�

UF researchers track genetic journey of HIV from birth to death

Tue, 16 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) GAINESVILLE, Fla. --- University of Florida scientists have discovered how HIV evolves over the course of a person�s lifetime into a more deadly form that heralds the onset of full-blown AIDS. The findings could pave the way for new therapeutic agents that target the virus earlier in the disease process, before it takes a lethal turn, researchers say.

�We were very interested in understanding how the virus mutates from the beginning of the infection until the end,� said Marco Salemi, an assistant professor of pathology, immunology and laboratory medicine in the UF College of Medicine and lead author on the study, which appeared in an online issue of the journal PLoS ONE in September. �Previously, the only thing known was that somehow the HIV population mutates. And as soon as that happens, patients start developing AIDS. But no one knew how and where the population evolved over time.�

To find out, UF researchers began tracking four children born with HIV, studying blood samples taken at birth, throughout life and just after death, when tissues samples were also taken. Using a high-resolution computational technique, they monitored mutations in a protein that helps HIV attach to human cells and then categorized the virus into two groups, R5 and X4. The R5 population is usually present in high numbers during the early stages of infection. But the X4 population enters the scene later, just before HIV gives way to full-blown AIDS. The researchers tracked the viruses in each patient to find out when and where the telltale X4 population first appeared.

�The general dogma has always been that the X4 viruses are more pathogenic than the R5 viruses. And that really isn�t true. People die from the R5 viruses,� said Maureen Goodenow, senior author of the paper and the Stephany W. Holloway university chair for AIDS research in the UF College of Medicine. �But certainly evolution of these X4 viruses is not a good prognostic indicator. So if we could understand the selective pressures that push viruses to develop like that, and the steps involved in the conversion of viruses, then we might be able to set up new targets for drug development.�

Previous studies have relied on cell culture or animal models to follow the virus� mutations over time. The UF researchers are among the first groups to study the progression of HIV in human patients.

As the study revealed new information about the evolution of HIV, UF scientists learned that most viral changes take place in the thymus, a small organ located behind the breastbone that is responsible for immune cell development.

�We found that the late-stage viruses, the X4 viruses, were localized predominantly in the thymus,� Goodenow said. �It says that the thymus is the place where these viruses develop, or at least where they�re localized and replicate.�

The origin of the X4 viruses has puzzled scientists for years. The UF research reveals that the X4 viruses are not present in the body all along, as some scientists had speculated, but rather, that they evolve directly from the R5 population just before the onset of AIDS. The researchers also found that HIV followed a similar path in each child, regardless of variations in the patients� medical histories.

�We�re starting to see what looks like a program of virus development over time. And it doesn�t matter who the person is. And it doesn�t matter what the time scale is,� Goodenow said. �It�s raising the possibility that, in fact, the evolutionary track of the virus is not totally random. There could be a real developmental program that the virus goes through.�

Eight years ago, when the National Institutes of Health-funded study began, pregnant women infected with HIV had few therapeutic options. But recent advances in prenatal drug therapies have substantially decreased the rates of mother-to-child transmission. The Centers for Disease Control and Prevention estimates that less than 2 percent of American mothers currently infected with HIV/AIDS will transmit the viruses to their babies during birth. Without the drugs, about 40 percent of infected mothers would give birth to babies with HIV.

Those therapies may help future children, but they came too late for the subjects enrolled in the study. The children received minimal medication and all developed full-blown AIDS by their first birthdays.

�Their whole virus infection was what we call the natural history,� Goodenow said. �This tells you what happens in the absence of combination antiretroviral therapy.�

The next step, Goodenow said, will be to track the evolution of HIV in adults before and after treatment. The researchers hope their findings will pave the way for new drugs that interfere with the virus� ability to evolve in the thymus.

�This is an excellent study that reveals fine-scale patterns in the evolution and adaptation of HIV during infection,� said Oliver Pybus, a research fellow in the department of zoology at Oxford University. Pybus was part of a team that, three years ago in Science, published descriptions of the high-resolution technique UF researchers used in their study. �For the first time, it shows how the movement of immune cells with the body is linked to the evolutionary behavior of the virus, which in turn determines the clinical outcome of infection.�

Darwin Symposium at Field Museum offers broad overview of his science and its impact

Tue, 16 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO�World-class experts from the United States and Great Britain will speak at The Field Museum for a one-of-a-kind symposium on Charles Darwin and his theory of evolution, which continues to excite the world and direct scientific research 125 years after Darwin�s death.

The free one-day symposium will be held Saturday, November 3, 2007, from 9:00 a.m. to 5:00 p.m. at The Field Museum�s James Simpson Theater. It will cover Darwin and his theory broadly and comprehensively and reveal new directions in cutting-edge research. At the same time, subject matter will be presented in clear terms that museum goers will be able to understand.

�We will be celebrating one of the great scientific revolutions of all time�as well as the person behind it,� said Neil Shubin, Field Museum Provost and Associate Dean for Organismal and Evolutionary Biology at the University of Chicago. �Darwin changed the way we think about our world and our place in it. This symposium is an opportunity to showcase some of the cutting-edge research that is currently underway in the variety of fields that Darwin impacted.�

Shubin will speak at the symposium about the origin of tetrapod limbs. A tetrapod is any vertebrate with four limbs (or four-limbed ancestors). It is a group of animals that includes the human being. Shubin made headlines around the world last year with the discovery of Tiktalik, a fishlike creature with limbs that allowed it to walk on land.

At this time with the theory of evolution under attack in some quarters, the public should strive to better understand Darwin and how his theory of evolution continues to provide a contextual framework for explaining all of life on earth, scientists say. �It is truly amazing that Darwin�s theory continues to hold up under the light of modern genetics and molecular biology,� said Olivier Rieppel, chair of The Field Museum�s Geology Department and Curator of Fossil Amphibians and Reptiles.

Darwin had no knowledge of genes whatsoever, yet some of the best evidence for his theories have come from genetics�a field that did not even exist at his time. Many of the talks will show how various diverse scientific disciplines, from molecular biology to medicine and genetics to paleontology not only support Darwin�s theories but also allow us to understand some of the key events in evolution.

�Darwin is an example of what the best science can do,� Shubin concluded. �A single idea can change the world and offer us new ways to see ourselves. In fact, as we learn more about our genome and those of other creatures, Darwin's theories become ever more relevant.�

The symposium coincides with the popular Darwin exhibition at The Field Museum that covers his life and his science. For information about this exhibition, which runs until January 1, 2008, see

Lack of HIV prevention for male sex workers in the Caribbean could fuel AIDS epidemic

Thu, 11 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Male sex tourists, largely from the United States and Europe, may be fueling an HIV/AIDS epidemic in the Caribbean, and efforts to stop the epidemic will be severely hampered unless HIV prevention dollars are diverted to help male prostitutes, a new study suggests.

Additionally, the study should serve as call to action for the tourism industry to implement HIV/AIDS prevention programs for tourists and tourism employees, said assistant professor Mark Padilla of the University of Michigan School of Public Health.

The Caribbean is second only to sub-Saharan Africa in HIV/AIDS cases. The disease has been described as primarily heterosexual, Padilla said. However, Padilla's book shows that sexual contact between Caribbean male sex workers and male tourists may be a much larger contributor to the HIV/AIDS epidemic there than previously thought.

Currently, prevention dollars in the Caribbean serve primarily heterosexuals, and this particular population of male sex workers who have sex with tourists is largely neglected. That population of male prostitutes grows larger as the traditional, agricultural jobs dry up. Funding comes from a variety of sources: governments, multilateral organizations such as the World Health Organization, and private foundations.

The Caribbean has become increasingly dependent on money from tourism, and young men have fewer options for making a living. Most male sex tourists in the study were from North America and Europe, Padilla said. The local men who served these tourists also had sexual encounters with female tourists, but Padilla's study did not directly examine that issue.

Many men are unemployed from rural areas, and they immigrate to tourism areas, Padilla said. Very few identify themselves as sex workers, and most have other income from tourism. Because of social stigma, these men often do not communicate with female partners about their involvement in sex work, which means the risk for HIV may be high among women.

The problem of why the bisexually behaving men do not come forth and are not reached by prevention programs is complicated, Padilla said. In Latin American culture, homosexuality is so stigmatized that men who engage in homosexual sex for money cannot speak out without becoming social pariahs. Many of them are married, but do not tell their wives about the prostitution or homosexual behavior. Many of these men do not use condoms consistently, especially with female partners, the study found.

Padilla said the tourism industry needs to be held at least partly responsible for providing a safer environment. Many of those tourism companies are based in the United States, he said.

The tourism industry needs to prioritize HIV prevention in any initiative they begin, he said. They should not be able to establish these massive tourism conglomerates without HIV/AIDS prevention and intervention programs.

They need to be aware that they are contributing to a sex economy that they are indirectly supporting, and to take responsibility to provide HIV prevention for these individuals, Padilla said.

Travelers can also lobby the industries directly, Padilla said. You can have an impact on the HIV epidemic simply by stating directly to your travel agency that you prefer a place with HIV prevention as a part of its company strategy. While there is little public information on the HIV prevention efforts of tourism companies, such questions by tourists may lead to greater attention to this issue.

Feline virus, antiviral drug studied to understand drug resistance

Wed, 10 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) COLUMBUS , Ohio �Researchers at Ohio State will spend the next two years testing their theories about just how an AIDS-like virus in cats is able to resist the powerful medicines that are thrown against it.

It's one of the latest efforts at understanding one of the leading problem areas in medicine today -- antimicrobial drug resistance. When bacteria or viruses become resistant to drugs, they become more difficult, or even impossible, to treat.

The project, funded by the National Institute on Drug Abuse, could reveal how some viral infections become able to withstand antiviral medications and even thrive in the presence of some drugs.

If successful, the research might pave the way to smarter, more effective treatments for a host of pathogens that have learned to resist most therapeutic efforts.

The project grew from important discoveries made five years ago as part of a controversial research program investigating the impact of methamphetamine on feline immunodeficiency virus (FIV) � one of only three animal viruses that can be used to mimick HIV (human immunodeficiency virus) infections in humans.

Surprisingly, that project showed that the virus was able reproduce itself 15 times faster when methamphetamine was present.

The work also showed that FIV mutated rapidly to adapt to grow in astrocytes, the dominant cell type within the brain, and that this phenomenon was accelerated by exposure to methamphetamine.

That observation led to an epiphany of sorts, explained Lawrence Mathes, professor of veterinary biosciences and associate dean for research and graduate studies in the College of Veterinary Medicine and principal investigator on the project.

�If the virus becomes drug-resistant as it routinely mutates into this new form, would that drug resistance occur earlier if methamphetamine were present� he asked.

After an initial phase five years ago that used cats as the animal model for the study, research shifted to more refined work with cell cultures of astrocytes grown in the laboratory, focusing on the changes taking place in individual cells. Mathes reasoned that the same mutated form of FIV would probably be present in the brains of infected cats.

He and his colleagues turned to tissue stored from another decade-old unrelated project that looked at how the virus suppressed the animals' immune systems.

�We went back to those tissues and, in fact, found that the same virus mutations we saw in the cultured cell experiments were present in that brain tissue but only after long-term infection,� he said.

The new research grant will use tissue culture methods to look specifically at how the presence of methamphetamine may increase the virus' ability to resist anitiviral drugs, in this case, a powerful AIDS drug called azidothymidine, or AZT.

�We know a lot about AZT, how it works and what mutations it causes in the virus,� he said. The researchers will treat FIV-infected cell cultures with low concentrations of AZT, forcing it to develop a resistance to the drug, repeating the procedure in the presence of methamphetamine.

�We know how long it normally takes the mutation to appear in the virus. We predict that it will appear earlier in cells exposed to both AZT and methamphetamine,� he said.

Mathes said that the first year of the project is focused on continued in vitro studies using both FIV and cat cell lines as well as parallel experiments with HIV in human cell lines.

If the results are promising, the researchers will test the drugs' interactions with the virus in a small study using two dozen cats in the second year.