A November 22 article in The New England Journal of Medicine
reported on a cohort of 1,028 HIV-infected children studied from 1996 through 1999.(1)
After statistical analysis to adjust for the fact that those starting treatment tended to be sicker, the study found that introduction of an antiretroviral regimen including a protease inhibitor was associated with a two-thirds reduction in risk of death (hazard ratio 0.33). The total reduction in death -- reflecting many treatment advances, not just antiretroviral therapy -- was more impressive: 5.3% mortality in 1996, 2.1% in 1997, 0.9% in 1998, and 0.7% in 1999. Both findings were highly statistically significant, p<0.001.
This study could not compare combinations including a protease inhibitor with combinations including an NNRTI (efavirenz, nevirapine, or delavirdine) because too few of the children were on NNRTI combinations -- only 3% in the last year of the study, 1999 -- compared to 73% on protease-inhibitor combinations, and 24% receiving only nucleoside analogs. But an accompanying editorial(2) noted that combination therapy with NNRTI drugs can achieve the same result. All the children were on antiretroviral therapy of some kind by 1999.
African American and Hispanic children were found to start therapy later. After statistical adjustment for severity of illness, this effect became less, and was no longer statistically significant. However, the authors suggested continued vigilance to ensure equitable access to treatment.
The authors also urged continued vigilance about the long-term risks of today's antiretroviral drugs when started in childhood; serious metabolic and other side effects have been seen in children as well as adults. This cohort study (PACTG 219) is continuing, and will be able to provide more information about long-term outcome and risk vs. benefit.
The accompanying editorial looked at treatment in developing countries. In the United States, the rate of HIV transmission from infected pregnant women to their children went from 25% to 1.4% with standard antiretroviral therapy; in those children who do get infected, beginning treatment in the first three months of life can stop viral replication completely and preserve normal immune function, provided proper treatment is continued. However, infrastructure in the developing world is just beginning to be created -- the United Nations AIDS Summit this year set a goal of only a 20% reduction in mother-to-child transmission by 2005. "Our efforts must focus on devising simple, relatively inexpensive, triple-combination regimens for the treatment of all HIV-1-infected pregnant women and all HIV-1-infected children. Such a regimen could be provided for $5 per day and would have a substantial effect on the prevention and treatment of HIV-1 disease in the developing world. These efforts would represent an important step toward changing the face of pediatric HIV-1 infection for the many millions who are affected by it around the world."(2)
- Gortmaker S.L., Hughes M., Cervia J., and others. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. The New England Journal of Medicine. November 22, 2001; volume 345, number 21, pages 1522-1528.
- Sullivan J.L. and Luzuriaga K. The Changing Face of Pediatric HIV-1 Infection. The New England Journal of Medicine. November 22, 2001; volume 345, number 21, pages 1568-1569.
Note: The abstract is available online to anyone at: http://content.nejm.org/cgi/content/short/345/21/1522. The abstract has links to the full text and the editorial -- but these are only available to subscribers to the Journal.
ISSN # 1052-4207
Copyright 2001 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.
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