RxPG News : Infectious Diseases

Shock therapy to eradicate Escherichia Coli

Thu, 12 Jan 2012 02:03:27 PST

( from http://www.rxpgnews.com ) According to a study published in the International Journal of Food Safety, Nutrition and Public Health, a short burst of low voltage alternating current can effectively eradicate E. coli bacteria growing on the surface of even heavily contaminated beef. The technique offers an inexpensive and easy to implement approach to reducing the risk of food poisoning, which can occur despite handlers complying with hygiene standards.

Escherichia coli (E. coli) is a bacterium that is commonly found in the gut of humans and warm-blooded animals. Most strains of E. coli are harmless. Some strains however, such as enterohaemorrhagic E. coli (EHEC), can cause severe foodborne disease. It is transmitted to humans primarily through consumption of contaminated foods, such as raw or undercooked ground meat products, raw milk and contaminated raw vegetables and sprouts.Infection with this bacterium causes serious diarrhea, dehydration, kidney problems and can lead to serious long-term problems or even be fatal in children, the elderly and people with pre-existing health problems. Tens of thousands of people are affected by E. coli infection each year through eating contaminated beef and other food products. The US Centers for Disease Control and Prevention (CDC) estimates that about 2500 people are hospitalized and there are several dozen deaths each year.

Now, Ajit Mahapatra and colleagues at Fort Valley State University, in Georgia and Virginia Tech have demonstrated that applying a low-voltage alternating current to beef samples inoculated with large numbers of the potentially lethal E. coli O157:H7 can almost completely deactivate the bacterium, which is usually present on the surface of contaminated meat. The team points out that the level of contamination used in their tests far exceeded the contamination that would be seen in commercial carcasses after slaughter.

Previous researchers had demonstrated that electricity can kill bacteria effectively. The study by Mahapatra and colleagues proves efficacy against E. coli O157:H7 at low voltage and low alternating current. It offers a quick and easy way to decontaminate at-risk, but otherwise safe beef without recourse to microbicidal chemicals or other more complicated treatment processes.

Risk of contracting diabetes to increase in world of 7 billion people

Mon, 14 Nov 2011 05:00:00 PST

( from http://www.rxpgnews.com ) World citizen number 7 billion is less likely to die from infectious diseases like measles or even AIDS, and more likely to contract diabetes or other non-communicable diseases (NCDs), as they are now the leading causes of deaths globally.

14th of November is official World Diabetes Day. In a world of 7 billion people with changing disease patterns, this day is more relevant than ever, according to external lecturer Siri Tellier from the Copenhagen School of Global Health at the University of Copenhagen.

Our new world citizen number 7 billion is more likely to grow up in an urban setting, which increases his or her risk of getting diabetes, as well as chronic obstructive pulmonary disease (COPD), cancer and heart disease, says Siri Tellier, who teaches demography and health in emergencies, while she also lectures on international perspectives on demographic challenges to Chinese university students in Beijing.

World citizen number 7 billion, who was estimated to be born on 31 October, will face very different diseases than that of children born only a few decades ago. As the population of urban areas keeps growing, it rapidly changes the global health challenges.

Until 2008, the majority of the world population lived in rural areas, but since then the majority has become urban, and most future population growth will happen in urban areas of developing countries. And one third of them, a little more than one billion, live in urban slums, says Siri Tellier.

A high proportion of people who move to cities are young adults, and this has several implications for health. Among them are the consequences of leaving their parents behind in rural areas.

Aging parents can no longer depend on their adult children for care. They will often 'live with' chronic NCDs such as diabetes, and will need daily assistance. It's not just a question of the children sending them money from their new home in a big city - who will care for the old people on a daily basis? The household size is shrinking. In rural areas it may be five, in urban areas only two. So in order to meet that challenge, new patterns of caring for older people will be needed, says Siri Tellier.

In the cities of the world, the health challenge is twofold: Firstly, living conditions in slum areas are poor, both with respect to water and sanitation, and access to health care almost non existent. In addition, life in urban areas often entails a shift toward 'modern' life styles, with inadequate nutrition, especially more fatty, salty foods, smoking, alcohol and lack of exercise - all primers for NCDs.

Secondly, when the young newcomers become parents, their own poor health will have influenced the unborn child's predisposition for NCDs.

Increasing numbers of studies show, that healthy ageing begins in the womb, Siri Tellier continues, and explains that if - for example - children are born with low birth weight, they are more likely to develop diabetes later in life

Our new world citizen nr. 7 billion will probably grow up in an urban setting, and will face factors that increase his or her risk of diabetes, as well as COPD, cancer and heart disease.

There is also an increasing awareness of the need to help even healthy, young people gain the habits which will predispose them for health in later life. Parents may have a hard time ensuring that their teenagers develops healthy habits, which will follow him or her throughout life, especially if a lack og these habits do not cause ill health immediately, Siri Tellier points out.

Of course, the good news is that the child is less likely to die from measles, or even AIDS or diarrhoeal diseases. We have reduced the number of child deaths from around 12 million in 1990 to less than 8 million today, and most of the saved lives are through prevention measures such as vaccinations against infectious diseases. That is not only good news, that is fantastic news. Siri Tellier explains.

Flemming Konradsen, Director of the Copenhagen School of Global Health at the University of Copenhagen, shares this optimistic view, and stresses that we must now deal with the non-communicable diseases as seriously as infectious diseases:

Global disease patterns are changing. As many countries around the world have reduced the great killers such as malaria, we must turn the same effort and resources towards NCD's, as they must be prevented now rather than treated later.

In addition to the personal consequences for the patient, NCDs burden developing health care systems with such high expenses, that can halt their development if we do not intervene, says Professor Flemming Konradsen.

NYUCN receives $7.56 million NIH grant to research heterosexuals at high risk of HIV infection

Fri, 28 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) New York University College of Nursing (NYUCN) received a five-year, $7.56 million grant from the National Institute on Drug Abuse (NIDA) at the National Institutes of Health (NIH) to evaluate the efficacy and cost-effectiveness of a peer-driven intervention to seek out heterosexuals at high risk for HIV in their communities, test them for HIV, and link them to care in a timely fashion if they are found to be HIV infected.

An estimated 25% of individuals currently living with HIV in the United States do not know they are infected. This undiagnosed HIV infection is particularly prevalent among populations that experience barriers to testing and care and that are therefore difficult to reach and engage. It is well documented that heterosexuals at high risk for HIV (HHR) are significantly less likely to test for HIV and more likely to be diagnosed with HIV late in the course of their HIV disease compared to their peers with traditional risk factors for HIV such as men who have sex with men and those who inject drugs. HHR also tend to experience serious delays in accessing care, placing them at grave risk for illness, loss of quality of life, and early mortality. People of color, particularly African Americans and Latinos, are vastly over-represented among the population of HHR.

The overall goal of this study is to develop a user-friendly, fairly brief, potent, and cost-effective method for reaching the population of HHR, and bringing those found to be infected with HIV into care in a timely fashion.

The problem of testing, treatment, and retention into care for HHR is challenging, because the population experiences a range of barriers to needed services. Among these are structural barriers, such as poor access to or difficulty accessing high-quality HIV testing and care; social barriers including social norms that do not encourage frequent use of health care generally, including of HIV testing; and numerous individual-level barriers such as mistrust of medical settings, fear of HIV testing, and not feeling at particularly high risk for HIV.

In fact, the prevalence of HIV infection among HHR in New York City has been found to be very high. Our research team, in collaboration with the New York City Department of Health and Mental Hygiene, has conducted surveillance with this population as part of the National HIV Behavioral Surveillance (NHBS) studies, led by Dr. Holly Hagan, a Professor at the College of Nursing. In the 2006-2007 study the NHBS found that over 7% of HHR in high-risk areas in New York City were infected with HIV, and only about 5% were aware of their diagnoses.

Even more striking, the NHBS study found that 11% of those in central Brooklyn were HIV-infected but did not know their status, said Dr. Marya Gwadz, a Senior Research Scientist at the College of Nursing, and the peer-driven intervention study's Principal Investigator. These findings inspired us to focus our efforts on this vulnerable population, and to concentrate on central Brooklyn, an area considered 'high risk' because of its elevated rates of poverty and a high HIV prevalence.

Gwadz and her research team, which includes Dr. Charles Cleland, Dr. Holly Hagan, Dr. Ann Kurth, and Dr. Noelle Leonard of the College of Nursing, and Dr. David Perlman of Beth Israel Medical Center, will build on the NHBS methodology, which uses a peer referral method called respondent driven sampling, to seek out and test HHR for HIV. Further, it will combine this recruitment method with peer education activities that can be conducted during the course of peer recruitment. These peer education activities are designed to increase an individual's motivation to join the study, be tested for HIV, and receive care in a timely fashion if HIV-infected. This is followed by patient navigation, an approach to support access to care, for those found to be HIV infected.

The peer-driven intervention is tailored specifically for African American and Latino HHR. We also designed it to be easy to use in the future in health departments and community-based organizations, by making use of computerized interactive components that don't require staff time to facilitate, peer-delivered components, which participants deliver independently, and patient navigation, a flexible and individualized approach to managing a complex health care system, said Dr. Gwadz. The project will enroll 3400 HHR in central Brooklyn over the course of five years.

The Department of Health has taken an active role in making sure all New Yorkers are offered HIV testing during medical encounters and then linked to care if they are found to be infected. Yet despite these efforts, the NHBS found that only a third of HHR had been tested in the past year. This suggests to us that in addition to the Department of Health initiatives we need active recruitment approaches to reach and engage people in their communities. Peer-driven interventions are powerful because they can simultaneously address both individual and social barriers, said Gwadz. Participants also like peer-driven interventions, because it provides them with a chance to give back to the community and help others access needed services.

The NHBS studies are the main surveillance efforts funded by the Centers for Disease Control and Prevention. These studies use both the peer referral method (respondent driven sampling), as well as individual recruitment of participants in select social venues at select times, called venue based sampling. While both of these recruitment methods have been effective in reaching vulnerable populations, no one has yet directly compared their effectiveness and relative costs for identifying undiagnosed HIV infection in HHR. One aim of this study is to answer this important research question and therefore provide guidance to the public health community on the costs and relative merits of each recruitment approach.

The study is designed to complement the vital local and national HIV prevention initiatives currently in place. We plan to contribute an efficient, innovative, and sustainable multi-level intervention to the HIV prevention portfolio at the end of the study, said Gwadz, as well as guidance on optimal approaches to reach HHR. Because the vast majority of HHR are African-American or Latino, we hope the study will ultimately play an important role in reducing racial/ethnic disparities in HIV/AIDS.

USAID awards cooperative agreement to CONRAD for multipurpose prevention study

Thu, 13 Oct 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Arlington, VA -- USAID awarded CONRAD a five year project with a $2 million ceiling to focus on testing the safety and effectiveness of the SILCS diaphragm, the one-size-fits-most contraceptive barrier, combined with tenofovir gel -- the only topical product proven to prevent the acquisition of HIV and Herpes Simplex Virus (HSV). If shown to be safe, effective and acceptable, this combination of products would provide women with a non-hormonal contraceptive method under their own control that also delivers protection against HIV and HSV. This award supports Aim 2 of USAID's Biomedical Research for Reproductive Health: to fast track development of reproductive health technologies that can simultaneously prevent unintended pregnancy, HIV, and other sexually transmitted infections.

Results of the SILCS diaphragm contraceptive effectiveness study were announced last month and showed effectiveness rates similar to that of a traditional fitted diaphragm. The benefits of this single size diaphragm include eliminating the need for a pelvic exam to fit the diaphragm, and meeting the contraceptive needs of women unable or unwilling to use a hormonal method.

In a recent landmark effectiveness trial conducted by CAPRISA in South Africa, tenofovir gel was shown to reduce the risk of HIV infection by 39% and HSV by 51%. Confirmatory studies of the gel are ongoing and will support regulatory approval.

Dr. Henry Gabelnick, CONRAD's Executive Director said, We see an urgent need for multipurpose prevention technologies, including non-hormonal methods that are easy to use, and that can be combined with a product that reduces the risk of HIV and HSV infection. This type of reproductive health technology is particularly needed in areas of the world where women need easy to use methods that are within their control.

Almost half of all pregnancies worldwide, estimated to be over 100 million annually, are unintended. In 2008, this resulted in 43 million abortions, half of which were performed under unsafe conditions, leading to almost 100,000 maternal deaths and 5 million women left with temporary or permanent disabilities. The majority of these deaths occur in less developed countries where the AIDS epidemic is most prevalent.

The SILCS diaphragm was developed at PATH, an international nonprofit organization whose mission is to improve the health of people around the world. PATH and CONRAD have collaborated on the validation of the SILC diaphragm for regulatory approval as a contraceptive device. CONRAD has been developing new methods of contraception for men and women for 25 years, including hormonal methods and barrier devices such as the female condom and cervical caps.

NIH modifies 'VOICE' HIV prevention study in women

Wed, 28 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A large-scale clinical trial evaluating whether daily use of an oral tablet or vaginal gel containing antiretroviral drugs can prevent HIV infection in women is being modified because an interim review found that the study cannot show that one of the study products, oral tenofovir, marketed under the trade name Viread, is effective.

An independent data and safety monitoring board (DSMB) recommended that the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study discontinue evaluating tenofovir tablets because the study will be unable to show a difference in effect between tenofovir tablets and placebo tablets. The DSMB found no safety concerns with oral tenofovir, which is currently used to treat HIV, or with the other products that will continue to be investigated as the VOICE study proceeds.

As the trial's primary sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, concurred with the DSMB's recommendation and will modify the study. Because the trial is continuing, the study data remain confidential and restricted to DSMB analysis. Given that data are unavailable, NIAID cannot speculate about why oral tenofovir did not show an effect among VOICE study participants.

Begun in September 2009, the VOICE study, or MTN-003, involves more than 5,000 HIV-uninfected women in South Africa, Uganda and Zimbabwe. The trial was designed to test the safety, effectiveness and acceptability of two different HIV prevention strategies: an investigational microbicide gel containing tenofovir, and oral tablets containing tenofovir either alone or co-formulated with the drug emtricitabine. The tablets, known by the brand names Viread (tenofovir) and Truvada (tenofovir plus emtricitabine), have been taken daily in an approach known as pre-exposure prophylaxis, or PrEP.

After its routine review of the study data on Sept. 16, the DSMB recommended that the investigators stop evaluating oral tenofovir because the study would be unable to show that tenofovir tablets have a different effect than placebo tablets at preventing HIV infection among the study participants. The DSMB therefore recommended that the roughly 1,000 women in the oral tenofovir group stop taking the study product. Further, the DSMB recommended that the VOICE study continue as designed to evaluate tenofovir gel and oral Truvada.

The study team will immediately begin to inform all VOICE participants of this new development and will soon begin the orderly discontinuation of the tenofovir tablets. Participants who were taking oral tenofovir will stop using the product at their next scheduled clinical site visit. They will then return eight weeks later for a final set of tests and procedures before exiting the study. At that visit, they will be provided information about where they can continue to receive HIV testing and counseling, contraception and other medical and support services.

NIAID is pleased that the trial will continue to examine the question of whether tenofovir gel and oral Truvada are safe and effective HIV prevention measures for women and thanks all participants in the VOICE study for their significant contribution to furthering HIV prevention research. This study is an important component of NIH's comprehensive HIV prevention research program articulated in the HHS National HIV/AIDS Strategy Operational Plan.

NIAID remains committed to supporting research to develop HIV prevention tools that women can implement. Slightly more than half of all new HIV infections globally occur in women, mostly through unprotected sex with HIV-infected men. A safe and effective microbicide or oral PrEP regimen would be particularly helpful to women when it is difficult or impossible for them to refuse sex or negotiate condom use with their male partners.

Scientists disarm HIV in step towards vaccine

Mon, 19 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have found a way to prevent HIV from damaging the immune system, in a new lab-based study published in the journal Blood. The research, led by scientists at Imperial College London and Johns Hopkins University, could have important implications for the development of HIV vaccines.

HIV/AIDS is the third biggest cause of death in low income countries, killing around 1.8 million people a year worldwide. An estimated 2.6 million people became infected with HIV in 2009.

The research shows that HIV is unable to damage the immune system if cholesterol is removed from the virus's membrane. Usually, when a person becomes infected, the body's innate immune response provides an immediate defence. However, some researchers believe that HIV causes the innate immune system to overreact and that this weakens the immune system's next line of defence, known as the adaptive immune response.

In the new study, the researchers removed cholesterol from the membrane surrounding the virus and found that this stopped HIV from triggering the innate immune response. This led to a stronger adaptive response, orchestrated by immune cells called T cells. These results support the idea that HIV overstimulates the innate response and that this weakens the immune system.

Dr Adriano Boasso, first author of the study, from Imperial College London, said: HIV is very sneaky. It evades the host's defences by triggering overblown responses that damage the immune system. It's like revving your car in first gear for too long. Eventually the engine blows out.

This may be one reason why developing a vaccine has proven so difficult. Most vaccines prime the adaptive response to recognise the invader, but it's hard for this to work if the virus triggers other mechanisms that weaken the adaptive response.

HIV takes its membrane from the cell that it infects. This membrane contains cholesterol, which helps to keep it fluid. The fluidity of the membrane enables the virus to interact with particular types of cell. Cholesterol in the cell membrane is not connected to cholesterol in the blood, which is a risk factor for heart disease but is not linked to HIV.

Normally, a subset of immune cells called plasmacytoid dendritic cells (pDCs) recognise HIV quickly and react by producing signalling molecules called interferons. These signals activate various processes which are initially helpful, but which damage the immune system if switched on for too long.

In collaboration with researchers at Johns Hopkins University, the University of Milan and Innsbruck University, Dr Boasso's group at Imperial have discovered that if cholesterol is removed from HIV's envelope, it can no longer activate pDCs. As a consequence, T cells, which orchestrate the adaptive response, can fight the virus more effectively.

The researchers removed cholesterol using varying concentrations of beta-cyclodextrin (bCD), a derivative of starch that binds cholesterol. Using high levels of bCD they produced a virus with a large hole in its envelope. This permeabilised virus was not infectious and could not activate pDCs, but was still recognised by T cells. Dr Boasso and his colleagues are now looking to investigate whether this inactivated virus could be developed into a vaccine.

It's like an army that has lost its weapons but still has flags, so another army can recognise it and attack it, he said.

Protecting adolescent girls from unwanted unprotected sex

Tue, 06 Sep 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Partner abuse leads to HIV infection, and black women are most at risk. A new study at the University of Pennsylvania School of Nursing has found that 46 percent of African-American adolescent girls report that their partner did not use a condom the last time they had sex -- often because of partner abuse. The girls described physical and sexual abuse and threats as preventing them from having their partner use condoms. The relationship between HIV and partner abuse is significant: In the U.S., at least 12 percent of HIV infections among women are a result of partner abuse.

Getting out of an abusive relationship should be considered an HIV prevention strategy, according to Anne M. Teitelman, assistant professor at the University of Pennsylvania School of Nursing, who published the study in the journal Advances in Nursing Science. Dr. Teitelman and her co-authors advocate the need for novel strategies to increase condom use among adolescents. The co-authors are Julie Tennille, MSW, LSW; Julia M. Bobinski, BSN, MS; Loretta S. Jemmott, PhD, RN, FAAN; and John B. Jemmott III, PhD.

Promoting healthy relationships among youth and preventing partner abuse in adolescent relationships should become a public health priority, writes Dr. Teitelman. This is necessary for primary prevention of the intersecting epidemics of partner abuse and HIV/STIs [sexually transmitted infections].

The study of 64 African-American adolescent girls, aged 14 to 17, illuminates the pressure a male partner may exercise to encourage girls to forgo condom use. Understanding the practice, which the authors term condom coercion, can inform more tailored prevention methods and interventions for adolescent girls at high risk for HIV and STIs, the authors report. Forms of condom coercion include physical and sexual abuse and threats, emotional manipulation, and condom sabotage, as when a male partner surreptitiously removes a condom.

Of the sample, 59 percent of girls experienced partner abuse that was physical, verbal, or threatening. Nearly 30 percent reported having unwanted vaginal sex and about 9 percent reported having unwanted anal sex. More than half the girls indicated they had experienced vaginal sex without a condom when they wanted their partner to use one.

When faced with partners trying to dissuade them from using condoms, girls may also feel pressures that silence them from even raising the topic of condom use. In the study, 25 percent of participants responded affirmatively to the question: Have you ever wanted to talk with your sexual partner about using a condom during vaginal sex, but were not able to?

This comment addresses the issue of silencing condom negotiation, which the authors define as girls' reluctance to voice an interest in condom use at the risk of losing the relationship or facing other negative consequences.

As one study participant reported: If we talk about just STIs and HIV, we're not addressing the whole picture. . . . I'm easily pressured into doing things that I don't want to do and it's hard to sit back at the time and ask myself, 'Is this something that I really want to do?' . . . oftentimes it's what he wants, but what I want . . . you don't want a baby, you don't want a STD, you don't want HIV. . . . do you want him to beat you up? . . . Don't let anybody tell you it's not about what you want, and he's going to be telling you that. There's always a way out of things, always.

Dr. Teitelman and colleagues are developing a clinic-centered intervention for girls based on their findings.

Genetic studies to explain the difference in susceptibility to the flu

Sat, 27 Aug 2011 20:06:27 PST

( from http://www.rxpgnews.com ) Why do some folks who take every precaution still get the flu, while others never even get the sniffles?

It comes down to a person's immune system response to the flu virus, says Alfred Hero, professor at the University of Michigan College of Engineering. In one of the first known studies of its kind, Hero and colleagues from Duke University Medical Center and the Duke Institute for Genome Sciences & Policy, used genomics to begin to unravel what in our complex genomic data accounts for why some get sick while others don't. The study findings appears in PLoS Genetics Aug. 25.

Hero's analysis group used several methods, including a pattern recognition algorithm previously developed for satellite imaging of the environment to discover the genomic signatures associated with immune response and flu symptoms. Using these genomic signatures, researchers compared the responses of previously healthy participants inoculated with the flu, and found significant and complex immune responses in both people who got sick and those who did not.

The gene expression data gets to the heart of how the immune system reacts and orchestrates its response to the flu virus, which dictates whether people get sick.

"We looked at over 22,000 genes in 267 blood samples," said Hero, who is also affiliated with the U-M College of Literature, Science & Arts and the U-M Medical School. "No study of this magnitude has ever been done on human immune response."

Geoff Ginsburg, study co-author and director of the Center for Genomic Medicine at the Duke Institute for Genome Sciences & Policy, said the study reveals what happens after virus exposure.

"It also points out, importantly, that remaining asymptomatic in the face of an exposure to a virus is an active process in the immune system, and we can now begin to probe the underlying biology to resisting infection," Ginsburg said.

The team inoculated 17 healthy individuals with the flu virus and about half of them got sick. They then collected gene expression data from each individual at 16 time points over 132 hours. These data provided a clear picture of the gene expression over time in those who developed flu symptoms and those who did not.

Eventually, if scientists can understand what happens at the level of the genome that makes people more or less susceptible to viral illness, they could potentially develop therapies to prevent the illness. Hero said the inflammatory genomic signature that differentiated the well group from the sick group was measurable up to about 36 hours before peak flu symptoms developed. It may, therefore, be possible to detect illness early, allowing people to take precautions and perhaps even prevent the worst symptoms.

Mathematical methods for finding hidden correlations within large quantities of data were a key component of the analysis performed by Hero and his former doctoral student Yongsheng Huang, who is lead author on the study. One of the principal analysis methods was a pattern-recognition tool previously developed for processing hyperspectral satellite images of the earth. Called Bayes Linear Unmixing, Hero applied it with virtually no modification to image the patterns of gene expression.

Research shows promise in the development of a vaccine against Chikungunya Virus

Sat, 13 Aug 2011 19:52:12 PST

( from http://www.rxpgnews.com ) Researchers have developed a new candidate vaccine to protect against chikungunya virus, a mosquito-borne pathogen that produces an intensely painful and often chronic arthritic disease that has stricken millions of people in India, Southeast Asia and Africa.

A single dose of the experimental vaccine protected lab mice from infection with the virus, according to a paper published online in the journal PLoS Pathogens by researchers from the University of Texas Medical Branch at Galveston, Inviragen, Inc., of Ft. Collins, Colorado, the University of Wisconsin, the Centers for Disease Control and Prevention and the University of Alabama.

"Currently, we have no approved treatment or vaccine for chikungunya, and there's a real need for an effective vaccine to protect against this debilitating and economically devastating infection," said Scott Weaver, director of UTMB's Institute for Human Infections and Immunity, scientific director of the Galveston National Laboratory and senior author of the paper. "Everything we've seen so far suggests this vaccine candidate could fill that need."

The experimental vaccine is a "recombinant live-attenuated vaccine" created by genetically modifying the chikungunya virus using techniques developed with the initial support from the Western Regional Center of Excellence in Biodefense and Emerging Infectious Diseases, headquartered at UTMB. The resulting vaccine strain differs from wild-type chikungunya virus in two ways: it doesn't cause disease, and it's incapable of infecting mosquitoes; the latter trait is an important safety feature to ensure that the vaccine strain cannot initiate transmission in nonendemic locations where travelers might be immunized before a trip to Africa or Asia. But it still provokes an immune response to protect against future chikungunya infections.

Such a live virus vaccine would also be relatively economical to produce in large quantities — an important factor given the limited resources available in the areas hit hardest by chikungunya.

"We need to slow this virus down in India and Southeast Asia, not just to protect the people there but to reduce the very real risk that it might become endemic here after an infected traveler arrives," Weaver said. "The best way to do that is with a vaccine, and if you're going to make a vaccine you have to look at where it's going to be used and what they can afford."

UTMB has signed a license agreement with Inviragen for commercialization of the new vaccine candidate. In addition, the two partners have been chosen to receive a four-year, $3 million grant from the National Institutes of Health to complete the preclinical development work needed submit an investigational new drug application to the Food and Drug Administration, opening the door to human trials.

International AIDS Society to launch Virtual Media Centre in July to support opioid substitution therapy in Eastern Europe and Central Asia

Tue, 19 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Tuesday, 19 July, 2011 (Rome, Italy) -- As a part of its new initiative, Expanding Access to Opioid Substitution Therapy (OST) for People Who Inject Drugs in Eastern Europe and Central Asia (EECA), the International AIDS Society (IAS) will launch a Virtual Knowledge Centre (VKC) in partnership with the Ukrainian Institute on Public Health Policy (UIPHP).

The announcement was made today at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011), which runs from 17-20 July in Rome and is being attended by more than 5,000 researchers, clinicians and community leaders.

The VKC initiative is a scaling up of the commitment by IAS to drug policy which it adopted as one if its four key priority areas in late 2010. Provision of OST, a call for expanded access to antiretroviral therapy (ART) for injecting drug users living with HIV, campaigning against the criminalization of injecting drug users, and a special focus on the EECA region underpin the policy. (1)

The VKC will strive to contribute to improved knowledge and strengthened operations research capacity for scale up of HIV/OST programmes for people who inject drugs by creating an increased Russian-language evidence base around OST, harm reduction and HIV, as well as specialized documents and training modules relevant to professionals, public health experts, narcologists, students, parliamentarians, NGOs and any other interested and involved parties working in this field in EECA. (2)

The IAS believes that evidence-based interventions are the best way to implement HIV treatment scale-up and will continue to advocate for expanding access to Opioid substitution therapy, said IAS governing Council member Chris Beyrer, who is the Director of the Johns Hopkins Center for Public Health and Human Rights in Baltimore, USA. The science has been in since the very beginning of the AIDS epidemic 30 years ago - OST and clean needle exchange programs save lives.

Outside of sub-Saharan Africa, injecting drug use accounts for approximately one in three new cases of HIV. In some areas of rapid HIV spread, such as in Eastern Europe and Central Asia, injecting drug use is the primary cause of new HIV infections. Legal barriers to scientifically proven prevention services such as needle and syringe programs and OST mean hundreds of thousands of people become infected with HIV and Hepatitis C every year. In Russia for instance some 60 per cent of new HIV infections are linked to injecting drug use and some 80 per cent of the one million people living with HIV are estimated to be less than 30 years of age. OST is illegal in Russia.

OST is proven to be one of the most effective methods of intervention, prevention and care for people who inject drugs and hence prevent the transmission of HIV. However, globally, treatment with methadone and buprenorphine reaches only eight per cent of injecting drug users. In 2007, only 2 per cent of injecting drug users in developing countries with injection-driven HIV epidemics was accessing treatment for Opioid dependence.

Many countries in the EECA regions have been slow to adopt human rights based public health approaches to illicit drug policy, despite compelling evidence that a human rights based policy and decriminalization of drug use is the most effective approach to decreasing HIV transmission and improving treatment outcomes.

Another major challenge is the criminalization and drug policy laws that many governments have in place. Because drug use is illegal, many local police forces increase surveillance near needle exchange programs or drug treatment facilities. This increased surveillance causes fear amongst drug users and increases syringe sharing while decreasing the amount of individuals seeking health-care. For those who are arrested or caught for illegal drug use, punishment includes harassment, beatings, or detainment.

It really is time to switch from criminality to care and put an end to registries, put an end to compulsory drug detention and ended the imprisonment for drug use/possession for personal use, said Patrizia Carrieri, a researcher at the French National Institute for Health and Medical Research (INSERM U912). Governments need to stop portraying drug users as less than human and therefore less deserving of their human rights and access to proper treatment and care.

In the Ukraine up to 75 per cent of people living with HIV are dying from tuberculosis, and prisons are becoming incubators of MDR-TB filled with people convicted for minor possession. Irina Borushek , an activist with the All-Ukrainian Network of People Living with HIV/AIDS is patient pointed out that the recent implementation of a high quality drug dependency treatment programme on which she herself is a patient, should become the norm, not the exception.

.Unless we make radical changes in drug policy, ensure effective scale up of drug comprehensive drug treatment, first of all, substitution treatment, and prioritize healthcare principles over repressive drug policy - we will fail to overcome HIV epidemic, said Borushek.

Liudmyla Sulga from the International HIV/AIDS Alliance in Ukraine and a Senior Lecturer in the School of Public Health at the National University of Kyiv-Mohyla Academy in Kiev said that law reform was an essential step if treatment was to be expanded across the Ukraine.

Alliance Ukraine is the largest NGO in the field of AIDS in Ukraine providing HIV prevention programmes to more than 240,000 people. The organization was instrumental in starting and rolling out medically assisted treatment for people who inject drugs.

In recent months however Alliance Ukraine has been lobbying to stop the systematic obstructions to the legal substitution treatment programmes for people who use drugs. Interference of law enforcement bodies into treatment programmes has created an atmosphere of fear for both patients and medical staff and has resulted in the failure to meet the National AIDS programme targets.

Further treatment programme expansion in the Ukraine will only be possible if there is a revision on drugs administration, using liquid forms of methadone and making drug administration and control more flexible for medical institutions, concluded Shulga.

NIH funds Emory-led consortium to advance AIDS vaccine research

Mon, 18 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) A consortium of leading vaccine researchers at Emory University and partner institutions has received a National Institutes of Health (NIH) grant aimed at developing an effective HIV/AIDS vaccine.

The five-year program project grant of more than $26 million from the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, will fund the Emory Consortium for AIDS Vaccine Research in Nonhuman Primates. The research will be conducted primarily at the Yerkes National Primate Research Center at Emory.

Developing a safe and effective preventive HIV/AIDS vaccine is still a critical part of the fight against this challenging disease that affects more than 30 million people worldwide, says Eric Hunter, PhD, who will lead the consortium.

With the vast experience of Emory's vaccine researchers and our partners, I'm confident we can make significant strides in developing a better HIV vaccine. Hunter is a member of the Emory Vaccine Center, a co-director of the Emory Center for AIDS Research, a professor of pathology and laboratory medicine at Emory University School of Medicine, and a Georgia Research Alliance Eminent Scholar.

The researchers will study how to develop a vaccine that can prevent the earliest stages of mucosal infection from simian immunodeficiency virus (SIV) in nonhuman primate models. SIV is similar to HIV in humans. The series of research projects is expected to provide a better understanding of how SIV is transmitted sexually and the specific immune responses HIV vaccines must generate in humans to block infection at mucosal sites, prevent the establishment of systemic infection, or dramatically reduce the pathogenic effects of infection.

The consortium's work will build on recent significant discoveries in the AIDS vaccine field. A vaccine trial in Thailand (RV144) completed in 2009 showed a modest degree of protection against HIV in humans. The results gave the vaccine research community hope that a vaccine could elicit antibodies that could at least moderately protect against HIV infection. In order to develop a more effective vaccine, however, researchers need to further explore the specific aspects of the immune response (referred to as correlates of immunity) in animal models as well as in human clinical trials, Hunter explains.

More than 90 percent of all HIV infections worldwide occur via mucous membranes, predominantly through sexual contact. In order to develop an effective vaccine, scientists must understand the viral-host interaction during the initial time of mucosal infection.

By the time HIV-infected individuals begin experiencing the symptoms of acute HIV infection, this critical time of opportunity has passed, says Rama Amara, PhD, co-principal investigator of the consortium and a researcher at the Emory Vaccine Center and Yerkes Research Center. Rhesus macaque monkeys provide an effective model for studying mucosal viral infection and ways to stimulate an early protective immune response.

Researchers agree that a successful HIV vaccine will likely need to elicit both effective T-cell and antibody responses. The Emory consortium will work to enhance the quality of antibody responses to HIV infection, building on recent Emory discoveries led by Amara and consortium member Bali Pulendran, PhD, using adjuvants to successfully enhance the effectiveness of vaccines against SIV infection.

Important follow-up questions the team will address include what kind of antigens and delivery system are needed to elicit protective antibodies, where should vaccines be delivered in the body, and how do adjuvants convert a poorly protective vaccine into one that fully protects against infection by the virus?

UNC tapped to lead national effort to find a cure for AIDS

Mon, 11 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) CHAPEL HILL, N.C. -- Researchers at the University of North Carolina at Chapel Hill have been awarded a $32 million, five-year federal grant to develop ways to cure people with HIV by purging the virus hiding in the immune systems of patients taking antiretroviral therapy. Tackling this latent virus is considered key to a cure for AIDS.

This is the first major funding initiative ever to focus on HIV eradication, and we at UNC are excited to lead this collaboration of an incredible group of 19 investigators from across the country, said David Margolis, MD, professor of medicine and microbiology and immunology in the UNC School of Medicine and principal investigator of this effort.

While previous HIV funding initiatives have focused on prevention and vaccine development, with this funding, the NIH and the scientific community are saying that finding a cure for AIDS is a realistic goal and should be part of our plan of attack against the epidemic, said Margolis, who is also professor of epidemiology in the UNC Gillings School of Global Public Health.

Although individuals infected with HIV may effectively control virus levels with antiretroviral drugs and maintain relatively good health, the virus is never fully eliminated from the cells and tissues it has infected. Researchers need to better understand where these reservoirs of HIV are located, how they are established and maintained, and how to eliminate them.

The National Institute of Allergy and Infectious Diseases (NIAID) grant will be administered by the North Carolina Translational and Clinical Sciences (NC TraCS) Institute at UNC and will be shared among researchers at nine U.S. universities, all of them pioneering researchers in HIV latency. Co-funding is also being provided by the National Institute of Mental Health (NIMH).

The UNC-led consortium will be one of three groups funded by NIAID under its Martin Delaney Collaboratory initiative. The UNC-led effort will undertake more than a dozen research projects to discover how the virus can remain dormant and virtually invisible, identify drugs and treatments capable of ridding the body of persistent infection and evaluate these new strategies in relevant animal models so that they can be translated into people.

This award will fundamentally change the way in which we look for a cure for AIDS, said Victor Garcia-Martinez, a UNC professor of medicine who is involved in the collaboratory.

Delaney was an internationally recognized AIDS activist who died in 2009. Delaney championed the concept of accelerating progress toward a cure for HIV infection through a public-private partnership involving government, academia and industry.

The UNC-led collaboratory also includes an important industrial partner, Merck Research Laboratories, Whitehouse Station, N.J. Merck has an outstanding track record in the development of small molecule drugs and other therapies that target viral reservoirs. Merck Research Laboratories will be receiving no federal funds for their contribution to this research.

This award takes a multidisciplinary approach to solve a very complex problem. It will allow for unique synergies and innovation that couldn't be accomplished otherwise, said collaboratory investigator Angela Kashuba, PharmD, associate professor in the UNC Eshelman School of Pharmacy and director of the UNC Center for AIDS Research Clinical Pharmacology and Analytic Chemistry Core.

All of the collaboratory members are inspired by the chance to change the natural course of HIV infection to achieve a cure or drug-free remission of this terrible disease, Margolis said.

The other universities involved in the UNC-led collaboratory are Case Western Reserve University; Johns Hopkins University; University of California, Davis; University of California, Los Angeles; University of California, San Diego; The Gladstone Institute; University of California, San Francisco; University of Minnesota, and the University of Utah.

Anti-HIV gel being evaluated in pregnant and breastfeeding women

Mon, 20 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) PITTSBURGH, June 20, 2011 -- Determining whether a promising HIV prevention gel is safe for women to use while they are pregnant or breastfeeding is the aim of a new clinical trial being conducted by the National Institutes of Health-funded Microbicide Trials Network (MTN). Researchers are hopeful that the study -- the first clinical trial of the vaginal microbicide tenofovir gel in breastfeeding women and only the second in pregnant women -- will bring them a step closer to developing a safe and effective HIV prevention product women can use throughout their lives.

The Phase I trial is underway at two U.S. sites -- Magee-Womens Hospital of the University of Pittsburgh Medical Center and the University of Alabama, Birmingham (UAB) -- but has implications for women throughout the globe. Indeed, nearly 16 million women are living with HIV worldwide, with most acquiring infection through unprotected vaginal sex. Microbicides, such as tenofovir gel, are products being developed to prevent HIV infection when used in the vagina or rectum. Researchers anticipate tenofovir gel may be the first vaginal microbicide approved for preventing HIV infection in women.

Tenofovir gel and other vaginal microbicides under development are intended to be used by sexually active women -- the very women most likely to get pregnant -- yet we have very little information about whether these products are safe for them to use, said Richard Beigi, M.D., M.Sc., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, who is leading the study.

In fact, HIV prevention may be most critical during pregnancy due to heightened immune responses or hormonal changes that appear to make pregnant women twice as likely to be infected by sexual partners. Most women also continue to be sexually active and use medication while they are pregnant and breastfeeding, so we need to know if products like tenofovir gel are safe for women and their babies before they become widely available, he added.

Promising results from an earlier clinical study of tenofovir gel called CAPRISA 004 found 39 percent fewer infections among HIV-negative women who used it before and after vaginal sex compared to women who used a placebo gel. A major large-scale study being conducted by the MTN called VOICE -- Vaginal and Oral Interventions to Control the Epidemic, is currently testing whether daily use of the gel, or an antiretroviral (ARV) tablet, can reduce risk for HIV among 5,000 women in southern Africa. The U.S. Food and Drug Administration (FDA) has indicated it will consider approving tenofovir gel as an HIV prevention method for women based primarily on its review of the results of CAPRISA 004 and VOICE, which are expected in 2013.

The new study, MTN-008, will provide critical information about the safety of using tenofovir gel during pregnancy and lactation, which the FDA also considers essential to its decision whether to approve the gel. The study is part of a comprehensive research program at the MTN designed to take incremental steps toward determining whether tenofovir gel can safely and effectively protect women against HIV infection when they are pregnant or breastfeeding.

Tenofovir gel contains the same ARV drug that in oral tablet form is a mainstay of one of the most widely used regimens for treating HIV. Oral tenofovir is increasingly being used, along with other ARVs, to safely treat both pregnant and breastfeeding women who are HIV-positive. Research also has shown that HIV-positive pregnant women who are treated with oral tenofovir pass very little drug to their newborn infants.

MTN-008 is a follow-up study to MTN-002, which found that a single dose of tenofovir gel given to pregnant women hours before scheduled Cesarean delivery was safe and well-tolerated by both mother and infant, resulting in only trace amounts of active drug in the mother's bloodstream, and in the amniotic fluid and umbilical cord blood. The drug levels measured in umbilical cord blood were 40 times lower than drug levels in studies of HIV-infected women who took the tablet form of tenofovir while they were pregnant. Building on these results, MTN-008 will test daily use of tenofovir gel by pregnant women for one week during third trimester pregnancy, and daily use of the gel for one week by breastfeeding mothers four to 26 weeks after they have given birth.

By taking a cautious, step-wise approach to this research, we are ensuring the safety of both mothers and their infants, said Dr. Beigi. Our overall goal is to find a product that women can safely use to protect against HIV during all stages of pregnancy and motherhood.

Researchers will enroll approximately 105 HIV-negative mother-infant pairs. For the pregnancy group, researchers will initially enroll 45 women between 37 and 39 weeks gestation and randomize them to receive tenofovir gel or a placebo gel. The women will apply one dose of their assigned study product (tenofovir gel or placebo gel) for seven consecutive days and undergo evaluation for side effects. Provided there are no safety concerns, researchers will then enroll a second group of 45 pregnant women who will follow the same seven-day regimen. The second group of women will enter the study earlier in their third trimester -- between 34 and 36 weeks gestation. For the group of breastfeeding women, all 15 participants who are enrolled will use tenofovir gel daily for seven days.

The researchers plan to evaluate the safety of the drug and assess how much active drug is absorbed during pregnancy and subsequently transferred to the fetus. In breastfeeding mothers, the researchers will also measure drug levels in breast milk and assess whether the drug is transferred to the baby. Depending on results of the study, which are expected in late 2012, the researchers will likely embark on a larger international trial involving a greater number of pregnant women, including those at earlier gestational ages.

Antibodies help protect monkeys from HIV-like virus, NIH scientists show

Thu, 05 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) WHAT: Using a monkey model of AIDS, scientists have identified a vaccine-generated immune-system response that correlates with protection against infection by the monkey version of HIV, called simian immunodeficiency virus (SIV). The researchers found that neutralizing antibodies generated by immunization were associated with protection against SIV infection. This finding marks an important step toward understanding how an effective HIV vaccine could work, according to scientists who led the study at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Scientists administered the SIV vaccine to half of the 129 monkeys in this study and a placebo vaccine to the other half. The scientists then gave each monkey up to 12 doses of one of two forms of SIV through rectal injection to simulate sexual exposure to the virus. The vaccine regimen did not protect the monkeys that received one form of SIV, but it reduced the rate of infection by 50 percent in the monkeys that received the other form of the virus.

To learn how the vaccine worked, the study team examined a variety of immune responses and certain genetic factors in the monkeys that the vaccine protected. The scientists found that SIV neutralizing antibodies and the activation of white blood cells known as helper CD4+ T cells correlated with the protective effect. Also, monkeys that expressed two copies of a gene known to help limit SIV replication were better protected by the vaccine than monkeys that did not, demonstrating that genetic factors can contribute to protection.

This study provides evidence that neutralizing antibodies are an important part of the immune response needed to prevent HIV infection. The ability of the vaccine regimen to protect monkeys from SIV infection is comparable to the results seen in the RV144 trial with 16,000 adult volunteers in Thailand; RV144 was the first HIV vaccine study to demonstrate a modest protective effect, reducing the rate of HIV infection by 31 percent. The new research also provides an animal model to better understand the immune basis for vaccine protection against lentiviruses, a subclass of viruses that includes HIV and SIV. This knowledge will help guide strategies for the future development of AIDS vaccines.

The SIV vaccine regimen used in this study was similar to an HIV vaccine regimen currently being tested in humans in the NIAID-funded clinical trial known as HVTN 505. Both vaccine regimens consist of priming with a vaccine made from DNA that encodes immunodeficiency virus proteins, followed by boosting with an inactivated cold virus (adenovirus) that contains immunodeficiency virus proteins.

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.

Prions transmitted through inhalation

Fri, 14 Jan 2011 22:20:29 PST

( from http://www.rxpgnews.com ) Airborne prions are also infectious and can induce mad cow disease or Creutzfeldt-Jakob disorder. This is the surprising conclusion of researchers at the University of Zurich, the University Hospital Zurich and the University of Tübingen. They recommend precautionary measures for scientific labs, slaughterhouses and animal feed plants.

The prion is the infectious agent that caused the epidemic of mad cow disease, also termed bovine spongiform encephalopathy (BSE), and claimed the life of over 280,000 cows in the past decades. Transmission of BSE to humans, e.g. by ingesting food derived from BSE-infected cows, causes variant Creutzfeldt-Jakob disease which is characterized by a progressive and invariably lethal break-down of brain cells.

It is known that prions can be transmitted through contaminated surgical instruments and, more rarely, through blood transfusions. The consumption of food products made from BSE-infected cows can also induce the disease that is responsible for the death of almost 300 people. However, prions are not generally considered to be airborne – in contrast to many viruses including influenza and chicken pox.

Prof. Adriano Aguzzi's team of scientists at the universities of Zurich and Tübingen and the University Hospital Zurich have now challenged the notion that airborne prions are innocuous. In a study, mice were housed in special inhalation chambers and exposed to aerosols containing prions. Unexpectedly, it was found that inhalation of prion-tainted aerosols induced disease with frightening efficiency. Just a single minute of exposure to the aerosols was sufficient to infect 100% of the mice, according to Prof. Aguzzi who published the findings in the Open-Access-Journal "PLoS Pathogens." The longer expo-sure lasted, the shorter the time of incubation in the recipient mice and the sooner clinical signs of a prion disease occurred. Prof. Aguzzi says the findings are entirely unexpected and appear to contra-dict the widely held view that prions are not airborne.
The prions appear to transfer from the airways and colonize the brain directly because immune sys-tem defects – known to prevent the passage of prions from the digestive tract to the brain – did not prevent infection.

Protecting humans and animals
Precautionary measures against prion infections in scientific laboratories, slaughterhouses and animal feed plants do not typically include stringent protection against aerosols. The new findings suggest that it may be advisable to reconsider regulations in light of a possible airborne transmission of prions. Prof. Aguzzi recommends precautionary measures to minimize the risk of a prion infection in humans and animals. He does, however, emphasize that the findings stem from the production of aerosols in laboratory conditions and that Creutzfeldt-Jakob patients do not exhale prions.

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

Community-based lymphatic filariasis education increases treatment compliance

Tue, 29 Jun 2010 18:11:00 PST

( from http://www.rxpgnews.com ) Community-based lymphatic filariasis education in Orissa State, India, increased treatment compliance from around 50% to up to 90%, according to a study published June 29 in the open-access journal PLoS Neglected Tropical Diseases. In their study, researchers from the U.S. Centers for Disease Control and Prevention, in partnership with the Church’s Auxiliary for Social Action, an India-based non-governmental organization, and IMA World Health, a US-based non-governmental organization, identified barriers to compliance with India's MDA program for LF, and suggest that timely educational and lymphedema management programs can reverse this trend.

Nearly 1.3 billion people worldwide live at risk of infection with the parasite that causes lymphatic filariasis. Infected individuals may develop long-term complications, such as grossly swollen limbs from lymphedema. Elimination of this disease of poverty requires giving drugs at least once per year to people who are at risk; of that population, 80% or more need to continue receiving medication on an annual basis for 5 or more years to stop transmission.

The authors evaluated a community-based education campaign, noted deficiencies, and designed interventions to correct them. An evaluation of the revised education program, covering over 8,000 people in ninety villages, showed markedly improved drug compliance and, for the first time, showed that lymphedema management programs, which teach leg care to patients with swollen legs, may also increase compliance with lymphatic filariasis mass drug administration programs. The increase was greatest in areas that had implemented U.S. Agency for International Development-supported programs to teach people how to care for legs swollen from infection.

This evaluation was confined to rural areas in Orissa State, so the findings do not necessarily apply to urban areas or areas outside the state. Nonetheless, lymphatic filariasis elimination programs facing difficulties in achieving the necessary level of drug compliance should consider evaluating their education campaigns using similar methods and integrating lymphedema management with lymphatic filariasis elimination efforts, the authors say.

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.

Disease control with current interventions has greater impact on malaria than global warming

Wed, 19 May 2010 14:45:44 PST

( from http://www.rxpgnews.com ) A study published today in the journal Nature casts doubt on the widely held notion that warming global temperatures will lead to a future intensification of malaria and an expansion of its global range.

The research, conducted by the Malaria Atlas Project (MAP), a multinational team of researchers funded mainly by the Wellcome Trust, suggests that current interventions could have a far more dramatic – and positive – effect on reducing the spread of malaria than any negative effects caused by climate change.

A steady stream of modelling studies have predicted that malaria will worsen and its range will spread as the world gets warmer. Malaria already kills more than a million people each year, mainly young children and pregnant women, with some 2.4 billion people at risk from its most deadly form.

Last year the Malaria Atlas Project produced a new map of modern-day malaria risk, giving researchers a unique opportunity to examine the effects that climate change may have had on the disease.

The new research compared this modern-day map with a historic reconstruction of malaria at its assumed peak, around 1900, and measured changes in the disease risk since that time. Although it is widely known that malaria has receded from many areas where it was previously endemic, such as the United States and much of Europe, the researchers were able to measure for the first time the extent of this recession and show that even in tropical areas the intensity of transmission has declined substantially this century.

The research was led by Dr Pete Gething from the Department of Zoology at the University of Oxford. He says: "The recession in malaria since 1900 is of little comfort to the billions of people still at serious risk, but it is important when thinking about the effects of climate on the future of the disease. We know that warming can boost malaria transmission but the major declines we've measured have happened during a century of rising temperatures, so clearly a changing climate doesn't tell the whole story."

The team compared the increases in malaria predicted by global warming scenarios with the actual declines of the twentieth century. Importantly, they also gauged the efficacy of different disease control measures when set against the possible adverse effects of rising temperatures and concluded that interventions such as insecticide-treated bed nets or modern antimalarial drugs can potentially outweigh the effects of global warming as much as tenfold.

Dr Simon Hay, who leads the MAP group in Oxford, explains: "When we looked at studies measuring the possible impact of bed nets or drugs, it was clear that they could massively reduce transmission and counteract the much smaller effects of rising temperatures.

"Malaria remains a huge public health problem and the international community has an unprecedented opportunity to relieve this burden with existing interventions. Any failure in meeting this challenge will be very difficult to attribute to climate change."

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.

Influenza predisposes to secondary bacterial infections

Sat, 23 Jan 2010 06:03:46 PST

( from http://www.rxpgnews.com ) Current research suggests that the flu may predispose to secondary bacterial infections, which account for a significant proportion of mortality during flu pandemics. The related report by Lee et al, "A mouse model of lethal synergism between influenza virus and Haemophilus influenzae," appears in the February 2010 issue of The American Journal of Pathology.

Influenza affects between three and five million people annually, causing up to 500,000 deaths worldwide. While most people will recover in one to two weeks, others will develop life-threatening conditions such as pneumonia or bronchitis. High-risk groups for seasonal influenza include the very young and old, people with compromised immune systems, and pregnant women. However, during influenza pandemics, mortality may be significant in previously healthy young adults.

A common complication of flu infection is a secondary "super-infection" by bacteria, which greatly increases the morbidity and mortality of the disease. The most common bacterial agents found following flu pandemics have been Streptococcus pneumoniae, Haemophilus influenzae, Group A Streptococcus, and Staphylococcus aureus. Furthermore, reports of infection with antibiotic-resistant strains have been increasing in recent years.

To explore the mechanisms governing the increased pathogenesis of flu upon super-infection, a group led by Dr. Sally R. Sarawar of the Torrey Pines Institute for Molecular Studies, San Diego, California confirmed that otherwise nonlethal influenza and H. influenzae infections cause high mortality rates in mice when flu infection precedes H. influenzae infection. Their data confirm a restricted time period for this heightened susceptibility and highlight that excessive bacterial, and not viral, growth is associated with increased lethality. The fact that this increased mortality was observed in both immunocompromised and immunocompetent mice suggests that even normal healthy people are at increased risk for complications following bacterial super-infection.

Lee et al suggest that the "lethal synergy between influenza virus and the bacterial respiratory pathogen, H. influenzae, is mediated by innate immunity. They observed that severe damage to the airways was an early event in the co-infected mice, eventually leading to death. This underscores the need for early antiviral and antibiotic treatment to combat severe disease in human patients and highlights the importance of vaccination and effective hygiene measures to prevent secondary bacterial infections during influenza infection. This new model will be useful for further investigating the mechanisms underlying severe disease caused by the interaction between influenza virus and bacteria, which may have resulted in numerous deaths during influenza pandemics and continues to constitute a significant clinical problem in susceptible individuals." Currently ongoing studies suggest that this model may also be useful for identifying target molecules for the development of novel therapeutic agents and strategies.

Helicobacter pylori may enhance immunity against tuberculosis

Sat, 23 Jan 2010 04:11:16 PST

( from http://www.rxpgnews.com ) It’s been implicated as the bacterium that causes ulcers and the majority of stomach cancers, but studies by researchers at UC Davis, Stanford University and the University of Pittsburgh have found that Helicobacter pylori (H. pylori) also may play a protective role, against the worldwide killer, tuberculosis (TB).

In an article appearing online Wednesday in PloS ONE, Jay Solnick, UC Davis professor of medicine and microbiology at the Center for Comparative Medicine and his co-authors report that H. pylori infection may enhance immunity against tuberculosis, a disease endemic in many parts of the world, and for which there is no effective vaccine.

“Here is a bacterium that we know is sometimes harmful and that is clearly associated with cancer,” Solnick said. “But it’s not that simple.”

Solnick explains that up until the 20th century, when public health improved and antibiotic use was widespread, virtually everyone was infected with H. pylori. That remains the case today in most developing countries, implying that H. pylori may have evolved with its human host because it confers some selective benefit.

“These new findings suggest that one such benefit may be that H. pylori provides protection against tuberculosis, and perhaps other infectious diseases as well,” he said.

Tuberculosis is second only to HIV as a cause of death due to a single infectious agent; one-third of the world's population is estimated to be infected with Mycobacteriyum tuberculosis. However, most indivdiuals do not show clinical symptoms of the disease, a form of infection commonly known as latency. Only one in 10 latent infections will progress to active tuberculosis disease.

“One explanation may be the presence of chronic infection of the stomach with H. pylori,” Solnick said. The findings also may eventually aid in managing TB, since H. pylori infection may help determine whether someone infected with TB gets a latent, asymptomatic infection or active disease.

The collaborative research effort began with the hypothesis that a person’s immune responses to individual infections are modified by the existence of other infections, said Sharon Perry, an epidemiologist at Stanford University, and the study’s lead author.

Early studies funded by the National Institutes of Health showed that a patient infected with H. pylori had elevated immune responses to TB antigens. Perry’s work expanded to test the hypothesis in patients from immigrant populations in Santa Clara County, then in households in Gambia and Pakistan, where TB is prevalent. In the two-year study, the researchers found that individuals exposed to TB who then progressed to active disease were less likely to be infected with H. pylori than those who were not infected with H. pylori. Protection against tuberculosis may have been a result of enhanced immune responses to TB antigens in those infected with H. pylori, since H. pylori induces expression of interferon gamma and other cytokines, which are important for immunity against viral and bacterial infections.

At this point, Perry and Stanford University professor Julie Parsonnet wanted to test the theory in non-human primates. They enlisted Solnick at UC Davis, in conjunction with JoAnne Flynn of the Department of Microbiology and Molecular Genetics and Immunology at the University of Pittsburgh School of Medicine.

With a grant from the Bill and Melinda Gates Foundation, Solnick, Parsonnet, and Flynn looked at the role of H. pylori in 41 monkeys challenged with TB. Again, the findings were striking. Of the 30 monkeys that tested positive for H. pylori, only 5 developed active TB, but 6 of 11 monkeys that were negative for H. pylori developed active disease.

“The one-disease, one-pathogen paradigm doesn’t tell the whole story,” said Perry. “It is incomplete as an explanation of the clinical outcomes of chronic infection. In fact, the thousands of organisms that live with us play a role in shaping our immune response to specific infections.”

Solnick cites the “hygiene hypothesis” as one possible explanation. That theory suggests that a reduction in exposure to infectious diseases can make the immune system less able to fight other challenges. Conversely, exposure to certain pathogens may aid immune response to other infections.

The authors acknowledge the findings are preliminary and propose several follow-up studies. First, Solnick, Parsonnet and Flynn have proposed research to test whether experimental infection of H. pylori will protect monkeys from TB, and whether it will enhance the protective effect of immunization. If successful, they will test a recombinant H. pylori strain that expresses TB antigens for possible immunization against TB. These studies will be performed in collaboration with Ondek Ltd, founded by Barry Marshall, who was awarded the Nobel Prize in 2005 for the discovery of H. pylori.

Caffeine intake in chronic hepatitis C patients associated with less liver fibrosis

Tue, 05 Jan 2010 13:41:39 PST

( from http://www.rxpgnews.com ) Researchers from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) determined that patients with chronic hepatitis C virus (HCV) who consumed more than 308 mg of caffeine daily had milder liver fibrosis. The daily amount of caffeine intake found to be beneficial is equivalent to 2.25 cups of regular coffee. Other sources of caffeine beyond coffee did not have the same therapeutic effect. Details of this study are available in the January 2010 issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.

Liver fibrosis or scaring of the liver is the second stage of liver disease and characterized by a degradation of liver function due to accumulated connective tissue. Past studies have looked at modifiable behaviors, such as coffee consumption, that mitigate the progression of liver disease. A number of studies have looked at the benefits of higher coffee intake with results that include: lower prevalence of chronic liver disease, reduced risk of hepatocellular carcinoma (liver cancer), and lower risk of death from cirrhosis complications. "From data collected to date it remains unclear whether coffee itself, or caffeine provides the beneficial effect," said Apurva Modi, M.D. and lead author of the current study that focuses on caffeine intake and its impact on liver fibrosis.

From January 2006 to November 2008 all patients evaluated in the Liver Disease Branch of the National Institutes of Health were asked to complete a questionnaire to determine caffeine consumption. Questions were asked pertaining to all sources of caffeine including regular and diet soft drinks; regular and decaffeinated coffee; black, green, Chinese and herbal teas; cocoa and hot chocolate; caffeine-fortified drinks; chocolate candy; caffeine pills; and medications with caffeine. Participants were asked about their frequency of caffeine consumption, which was quantified as never; 1-3 times per month; 1, 2-4, or 5-6 times per week; 1, 2-3, 4-5, and 6 or more times per day.

The analysis included 177 participants who were undergoing liver biopsy with a mean age of 51 years and mean body mass index (BMI) of 27.5. Of those in the cohort 56% were male, 59% Caucasian, 19% Black, 19% Asian, 3% Hispanic, and 68% had chronic HCV. Daily consumption of caffeine from food and beverages raged from none to 1028 mg/day with an average of 195 mg/day, which is equivalent to 1.4 cups of coffee daily. Most caffeine consumed came from regular coffee (71%) followed by caffeinated soda (13%), and black tea (4%). Repeated administration of the questionnaire within a 6-month period displayed consistent responses suggesting caffeine intake does not significantly change over time.

Patients with an Ishak fibrosis score of less than 3 had a mean caffeine intake of 212 mg/day compared with 154 mg/day for those with more advanced fibrosis. The Ishak fibrosis score is the preferred system that measures degree of liver scarring with 0 representing no fibrosis through 6 indicating cirrhosis. For each 67 mg increase in caffeine consumption (about one half cup of coffee) there was a 14% decrease in the odds of advanced fibrosis for patients with HCV. "Our data suggest that a beneficial effect requires caffeine consumption above a threshold of approximately 2 coffee-cup equivalents daily," noted Dr. Modi. The protective effects of consuming more than 308 mg of caffeine daily persisted after controlling for age, sex, race, liver disease, BMI and alcohol intake for all study participants.

Researchers further evaluated caffeine and coffee separately to determine the individual effect of each on fibrosis. Results showed that consumption of caffeinated soda, green or black tea was not associated with reduced liver fibrosis. However, a significant protective effect could have been missed due to small numbers, as 71% of total caffeine consumed came from coffee. Caffeinated coffee had the most pronounced effect on reduced liver fibrosis. The authors suggest that further research is needed to determine if the protective benefits of coffee/caffeine intake plateau at amounts beyond the daily consumption threshold.

Study into Rev protein which helps in the spread of the virus

Tue, 05 Jan 2010 13:22:46 PST

( from http://www.rxpgnews.com ) Professor Denis Archambault of the Department of Biological Sciences of Université du Québec à Montréal (UQAM), and doctoral student Andrea Corredor Gomez have made a major discovery in the field of molecular biology. They have unlocked some of the secrets of a viral protein, known as Rev, which is very different from other proteins of the same type studied to date. The results of their research were recently published in the prestigious Journal of Virology.

The Rev protein plays an essential role in the propagation mechanism of certain types of viruses within an organism. The work of researchers Archambault and Gomez Corredor focused on this protein, and more particularly on a structure called the "nuclear localization signal" (NLS). They used as a model the Rev protein of the bovine immunodeficiency virus (BIV), a retrovirus related to the AIDS virus in humans.

Retroviruses, like all other viruses, are characterized by an inability to multiply on their own. In order to reproduce, they require a living host cell. A cell has a cytoplasm and a nucleus at the centre. The nucleus contains nucleoli, or sub-compartments. It was already known that the Rev protein, produced in the cytoplasm, moves into the nucleus and nucleoli of a cell infected with certain retroviruses. By binding to the viral RNAs found in the nucleus, it contributes to the transition of an infection from the early to the late stage. To fulfil this primary function, the Rev protein must first be able to enter the nucleus. To do so, it needs a "key", its "NLS" composed of amino acids.

A different nuclear localization signal (NLS)

Over the years, several researchers have looked at the NLS in different Rev proteins. Until now, the study of these proteins demonstrated the presence of a monopartite NLS, i.e. an NLS comprising one continuous sequence of amino acids. Much to their surprise, Denis Archambault and Andrea Gomez Corredor discovered that the BIV Rev protein has a bipartite NLS – composed of two amino acid motifs separated by a sequence of additional amino acids – a world first for this type of protein in all retroviruses studied to date, including the AIDS virus.

In addition, although other types of protein contain a bipartite NLS, this newly discovered NLS does not match any other bipartite NLS identified until now, whatever the type of protein studied. Normally a bipartite NLS is composed of two amino acid motifs separated by a spacer sequence, which is either short (about 10 amino acids) or long (about 30 amino acids). In the BIV Rev protein, the NLS is atypical because of the length of the spacer sequence (neither long nor short) and the amino acid composition of that sequence.

Finally, the authors also identified a new type of nucleolar localization signal (NoLS) which allows the Rev protein to penetrate inside the nucleoli. Although the role of this localization is unknown, it is the first time this type of signal has been reported in proteins of cellular or viral origin.

A first step toward further discoveries

According to Denis Archambault, "What we have here is a Rev protein whose characteristics are very different from the other proteins of the same type that have been studied to date. Although our findings relate to basic research, our study demonstrates that it is possible to learn a lot about viruses, and in particular a virus of animal origin. We now have a specific model that will allow us to study further the relationship between the localization of a protein and its effect on the host cell, and possibly the entire organism."

Closing schools for short periods does not decrease infection rates

Wed, 30 Dec 2009 12:43:29 PST

( from http://www.rxpgnews.com ) Closing schools for less than two weeks during a flu pandemic may increase infection rates and prolong an epidemic, say University of Pittsburgh researchers in a study published ahead-of-print and online in the Journal of Public Health Management and Practice. The findings, developed from a series of computer simulations based on U.S. census data, indicate that schools may need to be closed for at least eight weeks in order to significantly decrease the spread of infection.

The value of school closures has been debated as a possible strategy to stem or slow the current H1N1 influenza pandemic. Indeed, hundreds of schools across the country have been closed at different periods during 2009 for fear the virus would spread more quickly if they stayed open.

"Although closing schools may seem like a reasonable way to slow the spread of flu, we found that it was not effective unless sustained for at least eight weeks after implementation," said study lead author, Bruce Lee, M.D., M.B.A., assistant professor or medicine, epidemiology and biomedical informatics, University of Pittsburgh. Closing schools quickly at the start of an outbreak was much less important than keeping them closed continually throughout the epidemic, he added.

According to study authors, short-duration school closures can increase transmission rates by returning susceptible students back to school in the middle of an epidemic when they are most vulnerable to infection.

The study also found that identifying sick students individually and keeping them from attending school had minimal impact on an epidemic. In addition, there were no significant differences between individual school closures and system-wide closures in mitigating an epidemic.

The study was based on an agent-based computer simulation model of Allegheny County, Pa., that represented the county's population, school systems, workplaces, households and communities. Simulations were based on the movement of residents each weekday from their households to designated workplaces or schools, and included 1.2 million people―200,000 of whom were school-aged children. The study also included more than 500,000 households and nearly 300 schools.

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:

Clinical trials of 2009 H1N1 influenza vaccines

Sun, 13 Sep 2009 13:38:09 PST

( from http://www.rxpgnews.com ) We are encouraged by reports that are now emerging from various clinical trials of 2009 H1N1 influenza vaccines, conducted by various vaccine manufacturers. We expect additional companies to announce their preliminary trial results shortly. The early data from these trials indicate that 2009 H1N1 influenza vaccines are well tolerated and induce a strong immune response in most healthy adults when administered in a single unadjuvanted 15-microgram dose. We congratulate the companies on these trials, which are an important part of the ongoing worldwide effort to develop vaccines to protect the public from 2009 H1N1 influenza.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, also is conducting clinical trials of 2009 H1N1 influenza vaccines, produced by Sanofi Pasteur and CSL Limited. The NIAID trials are testing two different dosages (15 micrograms versus 30 micrograms) and evaluating the immune response to one and two doses of these vaccines. More than 2,800 people are participating in ongoing NIAID trials of these vaccines.

We are pleased to note that preliminary analyses of early data from the NIAID trials align with the recently announced findings and those to be announced imminently by other companies in that both vaccines studied induced what is likely to be a protective immune response in most adults following a single dose in the same amount (15 micrograms) used in seasonal flu vaccines. Specifically, in blood samples obtained 8 to 10 days after vaccination

Among healthy adults who received a single 15-microgram dose of the Sanofi Pasteur vaccine, a robust immune response was measured in 96 percent of adults aged 18 to 64 and in 56 percent of adults aged 65 and older.

Similarly, among healthy adults who received a single 15-microgram dose of the CSL Limited vaccine, a robust immune response was measured in 80 percent of adults aged 18 to 64 and in 60 percent of adults aged 65 and older.

Additional data from the NIAID trials are forthcoming. However, on the basis of these strong early data, our results are consonant with other reports that a single 15-microgram dose of unadjuvanted 2009 H1N1 influenza vaccine is well tolerated and induces a robust immune response in healthy adults between the ages of 18 and 64. For adults aged 65 and older, the immune response to 2009 H1N1 influenza vaccine is somewhat less robust, as is the case with seasonal influenza vaccines.

We note that the slight discrepancies seen in our trials between the Sanofi Pasteur and CSL Limited vaccines may be due to technical differences in the preliminary measurement of the amounts of antigen in the doses used in the clinical trial lots and the relatively limited numbers of samples studied to date, as well as the fact that our data are drawn from a very early time point after immunization.

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."

Condom use reduces risk of contracting herpes simplex virus 2

Mon, 13 Jul 2009 15:40:29 PST

( from http://www.rxpgnews.com ) Condom use is associated with a reduced risk of contracting herpes simplex virus 2, according to a report based on pooled analysis of data from previous studies in the July 13 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Herpes simplex virus 2 (HSV-2) typically causes genital herpes, a chronic, life-long, viral infection. Although studies indicate that consistent condom use reduces the spread of HIV and other sexually transmitted diseases such as chlamydia and gonorrhea, the effectiveness of preventing the transmission of HSV-2 through condom use is less certain, according to background information in the article.

Emily T. Martin, M.P.H., Ph.D., of Children's Hospital Research Institute and the University of Washington, Seattle, and colleagues analyzed data from six HSV-2 studies to assess the effectiveness of condom use in preventing the virus. The studies included three candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational sexually transmitted infection (STI) incidence study and a behavioral STI intervention study. These yielded results from 5,384 HSV-2-negative individuals (average age 29) at baseline for a combined total of 2,040,894 follow-up days.

More than 66 percent of those who took part in the six studies were male, 60.4 percent were white, 94.1 percent were heterosexual and most reported no prior STIs.

A total of 415 of the individuals acquired HSV-2 during follow-up. "Consistent condom users [used 100 percent of the time] had a 30 percent lower risk of HSV-2 acquisition compared with those who never used condoms," the authors write. "Risk of HSV-2 acquisition decreased by 7 percent for every additional 25 percent of the time that condoms were used during anal or vaginal sex." The risk of acquiring the virus increased significantly with increasing frequency of unprotected sex acts. There were no significant differences found in condom effectiveness between men and women.

"Based on findings of this large analysis using all available prospective data, condom use should continue to be recommended to both men and women for reducing the risk of HSV-2 acquisition," the authors conclude. "Although the magnitude of the protective effect was not as large as has been observed with other STIs, a 30 percent reduction in HSV-2 incidence can have a substantial benefit for individuals as well as a public health impact at the population level."

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.

Tiny fly can keep dengue-causing mosquito in check

Tue, 09 Jun 2009 13:35:48 PST

( from http://www.rxpgnews.com ) The larvae of a tiny fly or midge can help decimate a number of invasive Asian tiger mosquitoes, that infect 50 to 100 million people with dengue fever every year in the tropics.

Once found only in tropical and sub-tropical regions of Southeast Asia, the Asian tiger

mosquito has now spread to Africa, the Americas, Australia, the Caribbean, Europe and the Middle East.

Midge larvae do not harm native mosquitoes, helping them survive, even though the invasive mosquitoes are better at gobbling up resources.

The researchers found inherent size differences between the mosquito species. The

tree hole - mosquito is larger than the Asian tiger mosquito, which makes it less vulnerable to predation from the small but voracious predatory midge.

Previous studies have found that the native mosquito larvae also adopt less 'risky'

behaviours than the invasive mosquito larvae, making them less susceptible to being eaten.

'Size is having a major effect in terms of how the prey are getting consumed,' said Barry Alto, medical entomologist with the State Natural History Survey at the University of Illinois -.

'This is another mechanism that allows the native mosquito to hang on and co-exist with the invasive mosquitoes in certain areas where predators are present,' Alto said.

The Asian tiger mosquito was first detected in the US in 1985 in a shipment of used tyres to a Texas port. Like the native mosquito, it lays its eggs in watery containers, including tyres.

Even if the water evaporates, a splash of rain and a supply of nutrients such as the microbes that feed on dead leaves are all that the larvae need to hatch and grow.

Like the yellow fever mosquito -, another invasive mosquito that

is now well established in the Americas, the Asian tiger mosquito can carry several viral diseases that afflict humans.

The interaction between predators and native and invasive mosquitoes is one of several

factors that may contribute to disease transmission, Alto said, according to a U of I release.

These findings were published in the British Ecological Society's Journal of Animal Ecology.

Analysis of a critical protein produced by the 2009 H1N1 influenza A virus

Sun, 24 May 2009 04:17:24 PST

( from http://www.rxpgnews.com ) In just two weeks from the time the first patient virus samples were made available, Singapore scientists report an evolutionary analysis of a critical protein produced by the 2009 H1N1 influenza A virus strain.

In the Biology Direct journal's May 20th issue, Sebastian Maurer-Stroh, Ph.D., and his team of scientists at the Bioinformatics Institute (BII), one of the research institutes at Singapore's Biopolis, also demonstrated the use of a computational 3-dimensional (3D) structural model of the protein, neuraminidase.

"Because we were working as a team, driven by the common goal to understand potential risks from this new virus, our group at BII was able to successfully complete this difficult analysis within such a short time," said Dr. Maurer-Stroh, BII principal investigator and first author of the paper.

BII's interactive 3D model is available at the following link: http://mendel.bii.a-star.edu.sg/SEQUENCES/H1N1/

With the 3D model, Dr. Maurer-Stroh and his team were able to map the regions of the protein that have mutated and determine whether drugs and vaccines that target specific areas of the protein were effective. Among their findings:

a. neuraminidase structure of the 2009 H1N1 influenza A virus has undergone extensive surface mutations compared to closely related strains such as the H5N1 avian flu virus or other H1N1 strains including the 1918 Spanish flu;
b. neuraminidase of the 2009 H1N1 influenza A virus strain is more similar to the H5N1 avian flu than to the historic 1918 H1N1 strain (Spanish flu);
c. current mutations of the virus have rendered previous flu vaccinations directed against neuraminidase less effective; and
d. commercial drugs, namely Tamiflu® and Relenza®, are still effective in treating the current H1N1 virus.

With the Biology Direct journal paper, the Singapore scientists have become the first to demonstrate how bioinformatics and computational biology can contribute towards managing the H1N1 influenza A virus.

"BII's H1N1 virus sequence study marks a significant milestone in the use of computational biology methods in understanding how the mutations of the fast evolving influenza virus affect immunogenic properties or drug response," said BII Director Frank Eisenhaber, Ph.D. "This information helps to develop a strategy for fighting the H1N1 virus and for organising an effective treatment for patients."

Other technologies to tackle the 2009 H1N1 Influenza A virus have been developed by scientists at Biopolis research institutes sponsored by Singapore's A*STAR (Agency for Science, Technology and Research). They include:

a chip that is able to quickly sequence or decode the genes in the flu virus and distinguish between the H1N1, seasonal, and mutated flu strains, at the Genome Institute of Singapore (GIS).
a microkit for the detection and identification of the flu virus strain within 2 hours, at the Institute of Bioengineering and Nanotechnology (IBN).
a molecular diagnostic assay to distinguish between the H1N1 and seasonal flu strains, at the Institute of Molecular and Cell Biology (IMCB).

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.

New drugs could counter antibiotic resistant hospital infections

Thu, 09 Apr 2009 15:59:35 PST

( from http://www.rxpgnews.com ) Washington, April 9 - Latest research findings that lack of sufficient phosphate in a bacterium could turn it into a killer could help develop new drugs to disarm the antibiotic resistant pathogens that cause serious hospital-acquired infections.

Pseudomonas aeruginosa, a bacteria that is a common cause of lung infections, also infests the intestinal tract of 20 percent of all Americans and 50 percent of hospitalised patients in the US.

It is one of the hundreds of bacteria that colonise the human intestinal tract, usually causing no apparent harm. It might even be beneficial to its host.

However, once the host is weakened by an illness, surgical procedure or immunosuppressive drugs, the bacteria can cause infection, inflammation, sepsis - and death.

Why P. aeruginosa can suddenly turn on its host has eluded researchers - until now. Scientists have long known that after an operation or organ surgery, levels of inorganic phosphate fall.

The study authors, led by scientists of University of Chicago -, hypothesised that phosphate depletion in the stressed intestinal tract signals P. aeruginosa to become lethal.

To test this theory, they let worms - feed on 'lawns' of P. aeruginosa and Escherichia coli grown in both low-phosphate and high-phosphate media.

Only the worms that ate P. aeruginosa with low levels of phosphate died. The researchers dubbed the phenomenon 'Red Death' since unexpected large red spots appeared on the worms before they died, according to an U-C release.

'These findings provide novel insight into the mechanisms by which P. aeruginosa is able to shift from indolent coloniser to a lethal pathogen when present in the intestinal tract of a stressed host,' said Alexander Zaborin, lead author of the study and a research professional at the U-C Department of Surgery.

'It is almost as if the bacterium sense when to strike,' said John Alverdy, study co-author and professor of surgery at the U-C Medical Center. 'That should come as no surprise since the bacteria are smart, having been around for two billion years.'

The study will be published in the April 14 issue of the Proceedings of the National Academies of Science.

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.

New Test to Establish In-Vivo Safety of Dengue Vaccine

Mon, 16 Feb 2009 16:36:10 PST

( from http://www.rxpgnews.com ) Washington, Feb 16 - Researchers have developed a test to determine whether vaccines against a virus that infects 100 million people annually, now ready for clinical trials, should really protect patients from infection, or would make it more dangerous for them.

'Our study shows that the new test is likely superior to the standard test in its ability to tell whether a patient's response to a vaccine is safe,' said Xia Jin, associate professor of medicine at the University of Rochester Medical Centre - and co-author of the study.

Cases of tropical, mosquito-borne dengue fever have been expanding globally for more than 50 years, with nearly a third of the human population in 100 countries now at risk of infection with the four types of dengue virus.

Infection with the dengue flavivirus, which is related to West Nile Virus and Yellow Fever, annually results in an estimated half a million hospitalisations and 22,000 deaths, mostly among infants, according to WHO.

After decades of absence in the US, the disease is causing illness again along the Texas-Mexico border, experts say and add that widespread dengue infection in the continental US is a real possibility.

A typical dengue infection confines a patient to bed for more than a week with fever and severe limb pains, but most recover. In less than five percent of cases, however, dengue hemorrhagic fever - and dengue shock syndrome -, often deadly complications, develop just as the fever breaks.

Mostly affecting babies between five and eight months, DHF causes victims to vomit and pass blood in their feces and urine. If diagnosed quickly, patients respond to intensive hospital treatment and fluids, but mortality can reach 15 percent when undiagnosed.

DSS comes when the infection has caused so much fluid to leak out of capillaries that there is not enough blood to supply organs. As of 2008, there were no antiviral drugs designed to treat dengue and no drug candidates in late-stage development, said an URMC release.

These findings were published in Clinical and Vaccine Immunology.

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.

PA-824 : Promising new drug for TB

Sat, 29 Nov 2008 03:43:40 PST

( from http://www.rxpgnews.com ) An international team of biochemists has discovered how an experimental drug unleashes its destructive force inside the bacteria that cause tuberculosis (TB). The finding could help scientists develop ways to treat dormant TB infections, and suggests a strategy for drug development against other bacteria as well.

A report describing the research, led by Clifton E. Barry, III, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is published in the Nov. 28 issue of Science. Dr. Barry's collaborators included scientists from NIAID and from the Novartis Institute for Tropical Diseases in Singapore.

One-third of the world's population is infected with Mycobacterium tuberculosis (M. tb), the bacteria that cause TB. "Currently, there are no drugs available that specifically target latent tuberculosis infections in which bacteria are present but are not actively dividing," notes NIAID Director Anthony S. Fauci, M.D. "Dr. Barry and his colleagues have now given us a detailed picture of how the candidate TB drug PA-824 is metabolized inside Mycobacterium tuberculosis. Their discovery is a promising step towards developing effective drugs against latent TB as well as other bacteria."

Previously, Dr. Barry and his collaborators found that M. tb mutants lacking a specific bacterial enzyme were resistant to PA-824, but at that time, they did not know the function of the enzyme.

"It took several years, but at last we were able to recreate in the test tube what happens inside mycobacterial cells when the bacterial enzyme, which we named Ddn, and a second bacterial component called a cofactor, interact with PA-824," says Dr. Barry. The key event in PA-824 metabolism, they found, is the production of nitric oxide (NO) gas. "This highly reactive molecule," he adds, "is akin to a bomb blast that kills the bacteria from within."

NO gas is produced naturally by certain immune system cells after they engulf M. tb or other bacteria. This is one way that people with healthy immune systems can contain M. tb infection. However, this natural immune response is not always enough to completely rid the body of TB bacteria. In essence, PA-824 performs similarly to the NO-producing immune cells--but the drug's effect is more specific and triggered only after it enters the bacteria.

The non-dividing M. tb bacteria characteristic of latent TB infections are walled off by immune cells that aggregate around the bacteria to form a body called a granuloma. Oxygen levels are low inside granulomas. In their latest research, the scientists observed that NO-generation during PA-824 metabolism is greatest when oxygen levels are low. This observation suggests how PA-824 may work against non-dividing M. tb.

PA-824 was originally designed to work best under aerobic, or oxygenated, conditions. With this new understanding of how the bacterial enzyme and cofactor act on PA-824 under low-oxygen conditions, Dr. Barry says, scientists can design drugs with a chemical structure similar to PA-824 but optimize them from the start to behave best under low-oxygen conditions. This work is already proceeding in the laboratory at NIAID and in partnership with collaborators from the Novartis Institute for Tropical Diseases in Singapore as well as with scientists from the Genomics Institute of the Novartis Research Foundation in San Diego.

Because humans have neither the bacterial cofactor nor any enzymes equivalent to Ddn, PA-824 has no effect on human cells. Conversely, many bacteria have enzymes in the same family as Ddn. Thus, says Dr. Barry, it is possible to envision new kinds of NO-generating drugs designed to interact with enzymes associated with other disease-causing bacteria as well.

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.

How household bleach fights bacteria

Sun, 16 Nov 2008 08:36:56 PST

( from http://www.rxpgnews.com ) Despite the fact that household bleach is commonly used as a disinfectant, exactly how it works to fight bacteria remained an open question. Now, a report in the November 14th issue of the journal Cell, a Cell Press publication, provides an answer.

The researchers found that hypochlorous acid, the active ingredient in bleach, causes the unfolding of proteins in bacteria in much the same was that heat stress or fever does. Those denatured proteins then clump together irreversibly into a mass in living cells, similar to what happens to proteins when you boil an egg, according to the researchers.

The bacteria aren't totally defenseless, however. Under those circumstances, a protein chaperone called heat shock protein Hsp33 springs to action, protecting proteins from the aggregation effect and increasing the bacteria's bleach resistance. Protein chaperones are generally defined as proteins whose function is to help other proteins.

" We found both in vitro and in vivo that bleach attacks proteins," said Ursula Jakob of the University of Michigan, Ann Arbor. "They lose structure much like they would under high temperature. Under those circumstances, the [Hsp33] protein is specifically activated to increase resistance." Jakob emphasized that this newly discovered mechanism is clearly one way bleach kills bacteria, but it may not be the only way.

Why would bacteria have a system specifically designed to deal with bleach?

" Hypochlorous acid is an important part of host defense," Jakob said. "It's not just something we use on our countertops."

In fact, the innate immune systems of mammals, and specifically immune cells known as neutrophils, release high concentrations of hypochlorous acid (aka bleach) upon recognizing microbial invaders. In addition, Jakob said, some evidence suggests that enzymes that produce bleach may help keep the bacteria in our guts in check.

The specific effects of hypochlorous acid on proteins help to explain why hydrogen peroxide is an inferior antimicrobial agent even though both chemicals are expected to act as strong oxidants, Jakob said. Hydrogen peroxide doesn't do much for your countertops, she said, because it doesn't provoke these effects on proteins.

Hsp33 also represents another example of an emerging concept in protein biology: that some proteins actually become activated through the act of partial unfolding. Indeed, chaperones react to stress by unfolding in the same way that other proteins do. Far from leaving them useless, however, that change in conformation is exactly what turns them on. " Usually, we think proteins need structure to be active, but here they must lose structure to be active," Jakob said.

As for whether the findings will have any practical implications, Jakob said she isn't yet sure. For instance, she has doubts that bleach could be made to work any more effectively than it does, particularly given that it works so rapidly and so well as it is even at low concentrations.

The findings in bacteria could perhaps offer new insight into the damaging effects of bleach on our own proteins, she added, noting that hypochlorous acid produced by the immune system has been suspected to play a role in chronic inflammation. The protein unfolding seen in bacteria might explain what the chemical agent is doing, perhaps yielding clues about what might be done to stop it.

Flu shot rates lag for adolescents at risk

Wed, 12 Nov 2008 14:36:53 PST

( from http://www.rxpgnews.com ) Washington, Nov 3 - The rates of flu vaccination for adolescents who suffer from asthma and other illnesses are still far too low, according to a recent study.

The research was led by Grace Lee at the department of ambulatory care and prevention at Harvard Medical School and Harvard Pilgrim Health Care. She is also the co-author of the study

'Influenza vaccination has been recommended for adolescents with high-risk conditions for well over a decade,' noted co-author Mari Nakamura, clinical fellow in paediatrics at Children's Hospital, Boston.

Each year, between 20 and 40 percent of children and adolescents come down with the flu. For children with certain high-risk conditions, this can lead to severe illness, hospitalisations, and in some cases, even death, said a Harvard press release.

Because of this, the Centre for Disease Control strongly recommends that all adolescents vulnerable to influenza complications get vaccinated.

The study charted vaccination rates from 1992 to 2002 for 18,703 adolescents with asthma, cardiac disease, immune system disorders and other high-risk conditions who received care at Harvard Vanguard Medical Associates and were insured through Harvard Pilgrim Health Care.

Investigators also identified medical visits for checkups and other preventive care that these adolescents had during flu seasons to determine whether there were missed opportunities for vaccination.

Vaccination rates improved during the study period, but only from eight percent to 15 percent. During the last four years of the study period, 1999 to 2002, only 11 percent of adolescents with high-risk conditions received vaccinations during all four seasons. Over 56 percent of adolescents received no flu vaccinations during this four-year period.

The study team concludes both patients and providers need to be part of any intervention strategy aimed at increasing vaccination rates among this population.

These findings were published in November issue of Paediatrics.

High-tech system to cut hospital infections by half

Wed, 12 Nov 2008 13:58:50 PST

( from http://www.rxpgnews.com ) London, Nov 6 - Hospital-based infections continue to be the number-two killer in the US after heart disease.

A new high-tech software programme developed by Tel Aviv University researchers will cut such infections by half.

Yehuda Carmeli professor at the Sackler Faculty of Medicine, Tel Aviv University -, has developed a system for preventing hospital epidemics.

'When a patient comes to the hospital for treatment, the natural barriers that protect them against infection are bypassed,' said Carmeli, also a physician at the TAU Sourasky Medical Centre.

'Intubations, IV lines, catheters and other common hospital procedures expose a patient's most delicate tissues to the world. If a patient is taking immunosuppressants, steroids, or antibiotics, this can be a dangerous cocktail, and infections are just waiting to attack,' he said.

Integrating basic sanitary procedures, his system uses the tools of high-tech communication email alerts, SMSs, and online communication to alert hospital staff of potential threats, according to a TAU release.

'We stopped 45 percent of the primary hospital-borne organisms that attack patients from spreading,' said Carmeli. He recently demonstrated his system at top medical centres at Ohio State University and Philadelphia's Temple University.

Carmeli advised general practitioners to use simple measures. For example, improved hand washing and hygiene techniques, an obvious first line of defence against infection, are not practiced regularly.

He advised nurses to keep an alcohol-based cream solution next to each patient's bed for ease of use. In some cases, visitors and nurses should wear masks and gloves when handling or visiting a patient.

These findings appeared in Antimicrobial Agents and Chemotherapy.

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.

Drug resistent TB deadlier, more common than suspected

Tue, 11 Nov 2008 13:59:52 PST

( from http://www.rxpgnews.com ) Washington, Nov 6 - 'Exclusively drug-resistant tuberculosis' or XDR-TB is a menacing public health problem that is even deadlier and more common than suspected.

XDR-TB patients are four times as likely to fail treatment and three times more likely to die than patients with other forms of multi-drug-resistant tuberculosis -, according to a recent study.

Researchers directly compared XDR-TB patients with those having MDR-TB to determine the differences in treatment outcomes and long-term survival rates.

Researchers also found that MDR-TB was 'a major threat to public health,' representing 2.7 percent of new TB cases in South Korea in 2004, up from 1.6 percent in 1994.

Since its public appearance in 2006, XDR-TB rekindled an urgent interest in preventing, fighting and containing TB. But little was known about how this variant changed the face of combating TB on all fronts.

'Treatment outcomes [of XDR-TB] have varied among studies, and data on long-term survival are still scarce,' wrote Tae Sun Shim, an associate professor at Asan Medical Centre, Seoul, South Korea, and a principal investigator of the study.

This 'is the largest report that we know of that compares patients with XDR-TB with other patients with MDR-TB to determine the impact of XDR-TB on treatment outcomes and long-term survival in mostly HIV-negative patients with MDR-TB.'

The study reviewed the medical records of more than 1,400 patients in South Korea with MDR-TB - from all national hospitals, Korean National TB Association chest clinics and select university hospitals.

Researchers found that patients with XDR-TB were significantly older than MDR-TB patients, were more likely to have a history of treatment with second-line TB drugs, and more likely to have a history of being treated for TB two or more times.

Perhaps the biggest public health threat associated with XDR-TB, however, is not its virulence, but the lack of information and treatment options that medical authorities have on which to draw, according to a release of the American Thoracic Society.

The collective dearth of knowledge was likened by Giovanni Battista Migliori, Morgan Richardson and Christopher Lange, co-authors of the accompanying editorial, to the proverbial blind men trying to describe an elephant - too big a task to accomplish with too little information.

The results were published in a November issue of the American Journal of Respiratory and Critical Care Medicine.

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

Media makes infectious diseases seem much worse

Mon, 03 Nov 2008 14:58:13 PST

( from http://www.rxpgnews.com ) Tornoto, Nov 3 - Popular media coverage of infectious diseases make them seem worse than they are, according to a new Canadian study.

Diseases that surface frequently in the print media -like bird flu - are considered more serious than similar diseases that do not receive the same kind of coverage, such as yellow fever, according to the research.

'The media tend to focus on rare and dramatic events,' said Meredith Young, co-author and graduate in the department of psychology, neuroscience & behaviour, McMaster University.

'When a certain disease receives repeated coverage in the press, people tend to focus on it and perceive it as a real threat. This raises concerns regarding how people view their own health, how they truly understand disease and how they treat themselves,' added Young.

'Another interesting aspect of the study is when we presented factual information about the diseases along with the names of them, the media effect wasn't nearly as strong,' said Karin Humphreys, a co-author and assistant professor at McMaster's.

'This suggests that people can overcome the influence of the media when you give them the facts, and so objective reporting is really critical,' Humphreys added.

Equally surprising, said Humphreys, is the fact that the medical students -who would have more factual knowledge about these diseases - were just as influenced by the media, despite their background, according to McMaster release.

Researchers chose 10 infectious diseases drawn from the Centre for Disease Control database. Five were medical disorders that have been highly prevalent in the recent print media -anthrax, SARS, West Nile virus, Lyme disease and avian flu -and five were medical disorders that have not often been present in current media: Tularemia, human babesiosis, yellow fever, Lassa fever and hantavirus.

Two groups of students, undergraduate and medical students, were asked to rate how serious, how prevalent, and how 'disease-like' various conditions were.

'We see that a single incident reported in the media, can cause great public concern if it is interpreted to mean that the potential risk is difficult to control, as with the possibility of a pandemic like in the case of Avian flu, and bioterrorism, as in the case of anthrax infection,' said Young.

Conversely, when participants were presented with the descriptions of the disease, without the name, they actually thought that the diseases which received infrequent media coverage -the control group -were actually worse.

These findings were published online in the Public Library of Science.

MRSA nasal screening not so important

Thu, 23 Oct 2008 14:19:44 PST

( from http://www.rxpgnews.com ) Three Virginia Commonwealth University epidemiologists are downplaying the value of mandatory universal nasal screening of patients for MRSA, arguing that proven, hospital-wide infection control practices can prevent more of the potentially fatal infections.

In a report published in the November issue of Infection Control and Hospital Epidemiology, the team, composed of internationally acclaimed epidemiologists Richard P. Wenzel, M.D., Gonzalo Bearman, M.D., and Michael B. Edmond, M.D., of the VCU School of Medicine, said "hospitals get more bang for their buck with evidence-based infection control prevention."

Some states, including Pennsylvania, Illinois, California and New Jersey, are mandating nasal screening for methicillin-resistant Staphylococcus aureus, or MRSA, in some hospitalized patients. MRSA is a strain of Staph bacteria that does not respond to penicillin and related antibiotics, but can be treated with other drugs.

"The key safety question today, since it is possible to reduce the total risk of hospital infections by half with a broad-based infection control program, is what is the incremental benefit of a component focusing on a single antibiotic-resistant pathogen?" said Wenzel.

Using epidemiological principles and focusing on deadly bloodstream infections, the team modeled a focused-screening program that was assumed to be effective in reducing MRSA rates by 50 percent and compared it to a hospital-wide program designed to reduce the rates of all infections by half.

According to Wenzel, chair of internal medicine at the VCU School of Medicine and immediate past president of the International Society for Infectious Diseases, MRSA infections cause only 14 percent of hospital infections, and investing huge resources into their control would be less effective than implementing programs that would reduce the burden of all infections by 50 percent.

Also in the model, the MRSA screening was inferior to the general infection control programs, preventing fewer infections, fewer deaths and was also less effective in reducing years of life lost from infections. The MRSA screening tests have false positives – leading to the isolation of patients who are non-MRSA carriers – as well as false negatives – missing some true carriers.

Further, the cost of nasal swabbing tests for all patients in a screening program was estimated to be two to three times that of adding additional infection control nurses for a broad infection control program.

The authors acknowledge that there are some instances in which MRSA screening and topical antibiotic treatment of nares of carriers may add incremental benefit to a hospital wide, evidence-based program. For example, in a patient going for open heart surgery who is a MRSA carrier, a post-operative infection would be devastating.

Wenzel and his colleagues' broad perspective is that a focused screening program would have made more sense in the late 1980s and early 1990s since MRSA was the key in antibiotic-resistant pathogen. However, in the last 15 years hospitals are facing multiple bacteria with broad resistance (Vancomycin-resistant enterococci, imipenam-resistant pseudomonas, totally drug resistant Acinetobacter and others), and efforts need to be broad based with a goal of reducing the overall burden of infections

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.

Biochips to speed up detection of infections

Mon, 25 Aug 2008 11:06:38 PST

( from http://www.rxpgnews.com ) London, Aug 23 - Manchester University scientists have developed a method for making protein chips that would enable quick detection of infections, quick testing of serious diseases and rapid discovery of new drugs.

Protein chips - or 'protein arrays' are objects like slides that have proteins attached to them and permit crucial data about the behaviour of proteins to be gathered.

Functional protein arrays could give scientists the ability to run tests on tens of thousands of different proteins simultaneously, observing how they interact with cells, other proteins, DNA and drugs.

As proteins can be placed precisely on a chip, it would be possible to scan large numbers of them simultaneously and also isolate the data bearing on individual proteins.

These chips would allow large amounts of data to be generated with the minimum use of materials - especially rare proteins that are only available in very small amounts.

The Manchester team of Jenny Thirlway and Jason Micklefield and Lu Shin Wong, said the technical challenges of attaching proteins in a reliable way have previously held back the widespread application and development of protein chips.

Current methods also require proteins to be purified first, which implies that the creation of large and powerful protein arrays would be hugely expensive in terms of time, manpower and money.

Manchester University researchers said they have found a reliable new way of attaching active proteins to a chip.

The attachment occurs in a single step in just a few hours - unlike with existing techniques - and requires no prior chemical modification of the protein of interest or additional chemical steps.

Researcher Jason Micklefield said: 'DNA chips have revolutionised biological and medical science. For many years scientists have tried to develop similar protein chips but technical difficulties associated with attaching large numbers of proteins to surfaces have prevented their widespread application.

'The method we have developed could have profound applications in the diagnosis of disease, screening of new drugs and in the detection of bacteria, pollutants, toxins and other molecules,' Micklefield added.

The new technique was published online in the Journal of the American Chemical Society -.

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."