Long-term experience with combination antiretroviral therapy that contains nelfinavir for up to 7 years in a pediatric cohort

OBJECTIVE. We sought to provide long-term data on the clinical, immunologic, and virologic response to highly active antiretroviral therapy in infants and children who are naive to protease inhibitors. METHODS. HIV-1-infected children who were naive to protease inhibitors were treated with a combination of nelfinavir and 2 nucleoside reverse transcriptase inhibitors (stavudine and lamivudine) in an observational, prospective, single-center study. Virologic failure-free survival was assessed by Kaplan-Meier analyses. The increase in CD4+ T cells during follow-up was estimated with a generalized linear model incorporating repeated measurements. RESULTS. Thirty-nine HIV-1-infected children were included and followed for a median period of 227 weeks (interquartile range: 108-275 weeks). The virologic failure-free survival rate was 74%, 66%, 58%, and 54% after 48, 96, 144, and 240 weeks, respectively. Children who experienced virologic failure in 48 weeks (or 96 weeks) were younger at baseline compared with the responders (0.8 vs 5.3 years). Eighteen children remained on the regimen for >5 years. All children, including the nonresponders, showed a sustained immunologic response. Grades 3 to 4 toxicity was observed in 2 patients only. Eleven developed clinically evident lipodystrophy. CONCLUSION. Combination therapy can be used safely in infants and children over a long period. Young age is strongly associated with virologic failure. Although the virologic response declined, immunologic parameters and clinical improvement were sustained up to 7 years, at the expense of lipodystrophy. Copyright © 2006 by the American Academy of Pediatrics.