Antiretroviral treatment for children with peripartum nevirapine exposure
Date
2010
Authors
Palumbo, P.
Lindsey, J. C.
Hughes, M. D.
Cotton, M. F.
Bobat, R.
Meyers, T.
Bwakura-Dangarembizi, M.
Chi, B. H.
Musoke, P.
Kamthunzi, P.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. Results: A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. Conclusions: Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. Copyright © 2010 Massachusetts Medical Society.
Description
Keywords
lamivudine plus zidovudine, lopinavir plus ritonavir, nevirapine, article, CD4 lymphocyte count, child, child development, child growth, clinical trial, cohort analysis, controlled clinical trial, controlled study, disease severity, drug safety, drug treatment failure, female, gene mutation, genotype, highly active antiretroviral therapy, HIV associated dementia, human, Human immunodeficiency virus infection, immune reconstitution inflammatory syndrome, infant, infection prevention, liver toxicity, major clinical study, male, outcome assessment, perinatal drug exposure, prediction, preschool child, priority journal, randomized controlled trial, side effect, single drug dose, tuberculosis, vertical transmission, Anti-HIV Agents, Anti-Retroviral Agents, Child, Preschool, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Infant, Infant, Newborn, Infectious Disease Transmission, Vertical, Kaplan-Meiers Estimate, Male, Nevirapine, Pregnancy, Pregnancy Complications, Infectious, Pyrimidinones, Ritonavir, RNA, Viral, Treatment Failure
Citation
New England Journal of Medicine
363
16
363
16