Nevirapine versus Ritonavir-Boosted Lopinavir for HIV-Infected Children
- 21 June 2012
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 366 (25), 2380-2389
- https://doi.org/10.1056/nejmoa1113249
Abstract
Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established. In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24. A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log10 copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P<0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06). Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.)Keywords
This publication has 17 references indexed in Scilit:
- Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapineProceedings of the National Academy of Sciences of the United States of America, 2011
- First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trialThe Lancet Infectious Diseases, 2011
- Low-Frequency HIV-1 Drug Resistance Mutations and Risk of NNRTI-Based Antiretroviral Treatment FailureJama-Journal Of The American Medical Association, 2011
- Strategies for Nevirapine Initiation in HIV‐Infected Children Taking Pediatric Fixed‐Dose Combination “Baby Pills” in Zambia: A Randomized Controlled TrialClinical Infectious Diseases, 2010
- Antiretroviral Treatment for Children with Peripartum Nevirapine ExposureThe New England Journal of Medicine, 2010
- Antiretroviral Therapies in Women after Single-Dose Nevirapine ExposureThe New England Journal of Medicine, 2010
- Morphologic and metabolic abnormalities in vertically HIV-infected children and youthAIDS, 2009
- Early Antiretroviral Therapy and Mortality among HIV-Infected InfantsThe New England Journal of Medicine, 2008
- Virologic Response to Potent Antiretroviral Therapy and Modeling of HIV Dynamics in Early Pediatric InfectionThe Journal of Infectious Diseases, 2007
- Impact of Protease Inhibitor-Containing Combination Antiretroviral Therapies on Height and Weight Growth in HIV-Infected ChildrenPEDIATRICS, 2001