Children with HIV infection were eligible for the study if they had not previously been exposed to antiretroviral agents (except for those used to prevent mother-to-child transmission of HIV), if they required treatment according to WHO criteria, and if their baseline level of plasma HIV type 1 (HIV-1) RNA was above 5000 copies per milliliter. Children (and their mothers) could not have had previous exposure to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) such as nevirapine or efavirenz (hereinafter referred to as an absence of exposure to nevirapine).
The children were stratified by age (2 to <6, 6 to <12, or 12 to 36 months) and randomly assigned in equal numbers to either nevirapine or ritonavir-boosted lopinavir, combined with zidovudine and lamivudine. Nevirapine was initially given in a dose of 4 mg per kilogram of body weight once daily for 14 days, with a dose of 7 mg per kilogram twice daily thereafter (the dose approved by the Food and Drug Administration). An amendment to the protocol (September 4, 2007) increased the nevirapine dose to 160 to 200 mg per square meter of body-surface area (once daily for 14 days, then twice daily) in line with newly instituted WHO recommendations.
Children were enrolled at one site in India and at nine sites across sub-Saharan Africa (four in South Africa and one each in Zimbabwe, Zambia, Malawi, Uganda, and Tanzania). The study was approved by the ethics review committee at each site, the Ministries of Health (where appropriate), and the institutional review board at each partner institution in the United States. Each child’s parent or legal guardian provided written informed consent. Study visits and laboratory testing were conducted as previously described.1 (link)All the authors vouch for the completeness and accuracy of the data presented. The study was conducted in accordance with the protocol, available with the full text of this article atNEJM.org . The antirectroviral drugs used in this study were donated by Abbott, Boehringer Ingelheim, and GlaxoSmithKline. Representatives of these three pharmaceutical manufacturers participated in early discussions of the trial design but not in final design decisions or in trial implementation or analyses.
The children were stratified by age (2 to <6, 6 to <12, or 12 to 36 months) and randomly assigned in equal numbers to either nevirapine or ritonavir-boosted lopinavir, combined with zidovudine and lamivudine. Nevirapine was initially given in a dose of 4 mg per kilogram of body weight once daily for 14 days, with a dose of 7 mg per kilogram twice daily thereafter (the dose approved by the Food and Drug Administration). An amendment to the protocol (September 4, 2007) increased the nevirapine dose to 160 to 200 mg per square meter of body-surface area (once daily for 14 days, then twice daily) in line with newly instituted WHO recommendations.
Children were enrolled at one site in India and at nine sites across sub-Saharan Africa (four in South Africa and one each in Zimbabwe, Zambia, Malawi, Uganda, and Tanzania). The study was approved by the ethics review committee at each site, the Ministries of Health (where appropriate), and the institutional review board at each partner institution in the United States. Each child’s parent or legal guardian provided written informed consent. Study visits and laboratory testing were conducted as previously described.1 (link)All the authors vouch for the completeness and accuracy of the data presented. The study was conducted in accordance with the protocol, available with the full text of this article at
