Balancing Antiretroviral Therapy in Children
May 12, 2005, 18:02, Reviewed by: Dr.
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"While it is possible to celebrate the tremendous change in the outcomes of HIV-infected children treated with HAART, it is even more important to continue to prioritize research for the survivors who are now living with a chronic disease. The notion that the problem of HIV in children has been resolved is false-indeed, 15,000 to 20,000 perinatally-infected children and adolescents still need answers to problems such as salvage therapy, long-term complications from the disease or from ART, neurodevelopmental complications, and the ongoing need for new and simplified treatments. It would be a mistake to reduce funding for clinical research on HIV-infected children living in the United States, because such research might not only help these children but also contribute to the care of HIV-infected children worldwide who are starting to benefit from ART and who, in the near future, undoubtedly will develop the same problems that U.S. children are now experiencing"
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By JAMA,
There often is a short lag between the release of a new treatment for pediatric HIV infection and its implementation in the community, according to a study in the May 11 issue of JAMA.
Antiretroviral therapy (ART) for pediatric human immunodeficiency virus (HIV) infection has evolved from the single or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens of the 1980s and early 1990s to today's complex regimens of NRTI in combination with protease inhibitors (PIs) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs), according to background information in the article. No previous studies have examined how novel therapies have been integrated into the clinical care of pediatric HIV infection, or if there is concordance between recommended guidelines and treatment in clinical practice.
Susan Brogly, Ph.D., of the Harvard School of Public Health, Boston and colleagues examined the changes in the treatment of pediatric HIV in the United States from 1987 to 2003. The study included 766 perinatally HIV-infected children from the Pediatric AIDS Clinical Trials Group 219C cohort born before January 1, 2004, who had not participated in an ART clinical trial.
The researchers found that single and dual NRTI regimens were used most frequently through 1997. In 1998, 2 years after protease inhibitors were approved for adult HIV infection and at the time pediatric guidelines were issued, regimens of highly active antiretroviral therapy including a protease inhibitor became most frequently used. From 1998-2003, 22 percent of children initiated ART with a regimen not recommended by pediatric guidelines. In additional analysis, the risk of switching decreased with age at ART initiation and increased with year of initiation. The risk of switching was higher in children who started with 1 or 2 NRTIs or an unconventional regimen vs. children who started on a protease inhibitor-containing regimen.
"The use of unorthodox regimens not recommended by the U.S. pediatric guidelines was relatively common, and was related to a shorter time to first regimen switch," the authors write. "Monitoring and documenting ART use in HIV-infected children can provide important insight regarding the clinical care of this population."
(JAMA. 2005;293:2213-2220.)
For funding/support information, please see the JAMA article.
MORE ADVANCED, EARLIER TREATMENT OF PERINATAL HIV ASSOCIATED WITH DECREASED HIV PROGRESSION, BETTER OUTCOMES
In a related study in this week's JAMA, earlier treatment of children with HIV infection with ART is associated with less HIV progression and improved survival rates.
Worldwide, approximately 2.5 million children are infected with HIV, and approximately 1,700 new perinatal infections occur daily, according to background information in the article. In the United States, more than 9,300 HIV-infected children younger than 13 years have progressed to AIDS as of December 2003. While the Pediatric AIDS Clinical Trials Group (PACTG) 076 regimen has reduced perinatal transmission by 67 percent, prenatal combination ART has further reduced transmission to 2 percent or less. However, the impact of treatment on progression of perinatal HIV infection remains poorly characterized at the population level. Perinatal HIV infection may progress in 2 patterns: early, with a typical onset of age 4 months, or late, with a typical onset of age 6 years.
David R. Berk, M.D., of the Stanford University School of Medicine, Stanford, Calif., and colleagues conducted a study to determine the progression of HIV, survival, and distribution of category C (the most severe of three categories, dependent on symptomatic conditions) diagnoses in a perinatal population-based sample during different eras in prevention and management and in relation to early institution of any ART therapy. The researchers examined the trends in early progression of perinatal HIV infection among 205 HIV-infected children in Northern California born between January 1, 1988, and December 31, 2001, and followed up through age 3 years.
The researchers found that of 205 children, 134 (65 percent) received ART and/or prophylactic treatment against Pneumocystis jiroveci pneumonia. By age 3 years, 81 (40 percent) progressed to a category C diagnosis, 41 (51 percent) of whom died. Untreated children were significantly more likely to progress to a category C diagnosis (62 percent [44/71] untreated vs. 28 percent [37/134] treated children); none of 23 infants who received triple ART progressed to category C. However, even without triple ART, very early mono/dual ART (by age 2 months vs. 3-4 months) was associated with delayed and decreased progression to category C. Of 33 children born between January 1, 1996, and December 31, 2001, only 7 (21 percent) progressed to category C (compared with 1988-1995), 6 of 7 of whom received no therapy. More recent year of birth and more advanced therapy were associated with improved survival.
"There are few data to guide time to initiation and selection of therapy among young children with perinatal HIV infection. Our novel finding of improved outcomes even with mono/dual ART begun by age 2 months vs. 3 to 4 months, though limited by the small sample size, suggests the importance of very early diagnosis and treatment and is consistent with small clinical trials demonstrating a short-term protective effect of early vs. delayed ART among perinatally infected infants. Initiating ART within the first 2 months offers the potential to begin therapy during or near the time of primary infection," the authors write.
(JAMA. 2005;293:2221-2231.)
This study is supported by funding from the Office of AIDS, California Department of Health Services.
EDITORIAL: BALANCING THE UPSIDE AND DOWNSIDE OF ANTIRETROVIRAL THERAPY IN CHILDREN
In an accompanying editorial, Ram Yogev, M.D., of Children's Memorial Hospital, Chicago, comments on the HIV studies in this week's JAMA.
"While it is possible to celebrate the tremendous change in the outcomes of HIV-infected children treated with HAART, it is even more important to continue to prioritize research for the survivors who are now living with a chronic disease. The notion that the problem of HIV in children has been resolved is false-indeed, 15,000 to 20,000 perinatally-infected children and adolescents still need answers to problems such as salvage therapy, long-term complications from the disease or from ART, neurodevelopmental complications, and the ongoing need for new and simplified treatments. It would be a mistake to reduce funding for clinical research on HIV-infected children living in the United States, because such research might not only help these children but also contribute to the care of HIV-infected children worldwide who are starting to benefit from ART and who, in the near future, undoubtedly will develop the same problems that U.S. children are now experiencing," Dr. Yogev writes.
(JAMA. 2005;293:2272-2274.) 
- May 11 issue of JAMA.
JAMA. 2005;293:2213-2220.
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