Purpose of the Study. Combination antiretroviral therapy (highly active antiretroviral therapy [HAART]) has been shown to be effective in the management of adults with human immunodeficiency virus (HIV) disease. However, only limited data regarding the benefits to children and adolescents are available. The objective of this study was to assess the effect of HAART on the mortality of children with HIV infections.
Methods. A cohort of 1028 HIV-infected children and adolescents from birth through 20 years of age were followed in Pediatric AIDS Clinical Trials Group Protocol 219. Subjects were enrolled before 1996 and were followed prospectively through 1999. Proportional-hazards regression models were used to estimate the effect of combination antiretroviral therapy on mortality in this cohort.
Results. In 1996 only 7% of subjects were receiving combination therapy, but by 1999 73% were receiving such therapy which included protease inhibitors. Mortality declined dramatically from 5.3% in 1996 to 2.1% in 1997, 0.9% in 1998, and 0.7% in 1999 (P for trend < .001). Reductions in mortality were noted in all subgroups defined by age, sex, CD4+ lymphocytes at initiation of therapy, educational level of the parent or guardian, and race or ethnic background.
Conclusion. Combination antiretroviral therapy has markedly reduced the mortality among children and adolescents infected with HIV.
Reviewer’s Comments. This carefully conducted prospective study of children treated with “HAART” reveals the dramatic, albeit relatively short-term, improvements in mortality in children and adolescents with HIV. The findings clearly justify the use of such combinations in infected children. However, although combination antiretroviral therapy delays mortality, it is unlikely in its current form to have this effect indefinitely. Many patients have been treated with multiple combinations over years and are now highly resistant to many or most of the drugs available to them. Further, as long-term adverse effects of combination therapy become apparent, the benefits to individual patients will likely be compromised. The need for simpler, safer, and more potent agents is apparent. Further, the harnessing of the host immune response to control HIV replication indefinitely must be achieved if normal life expectancy and quality-of-life are to be expected for our HIV-infected children.
- Copyright © 2002 by the American Academy of Pediatrics