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Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure
Paul Palumbo, M.D., Jane C. Lindsey, Sc.D., Michael D. Hughes, Ph.D., Mark F. Cotton, M.Med., Ph.D., Raziya Bobat, M.D., Tammy Meyers, M.D., Mutsawashe Bwakura-Dangarembizi, M.D., Benjamin H. Chi, M.D., Philippa Musoke, M.B., Ch.B., PortiaKamthunzi, M.D., Werner Schimana, M.D., Lynette Purdue, Pharm.D., Susan H. Eshleman, M.D., Ph.D., Elaine J. Abrams, M.D., Linda Millar, B.A., Elizabeth Petzold, Ph.D., Lynne M. Mofenson, M.D., Patrick Jean-Philippe, M.D., and Avy Violari, F.C.Paed.
From Dartmouth Medical School, Lebanon, NH (P.P.); Harvard School of Public Health, Boston (J.C.L., M.D.H.); Tygerberg Children’s Hospital,Stellenbosch University, Tygerberg (M.F.C.); and Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban (R.B.) — both in South Africa; Harriet Shezi Children’s Clinic, Chris Hani Baragwanath Hospital, University of the Wit watersrand (T.M.), and the Perinatal HIV Research Unit (A.V.) — both in Johannesburg; the Department of Paediatrics and Child Health, University of Zimbabwe College ofHealth Sciences, Harare, Zimbabwe (M.B.-D.); Centre for Infectious Disease Research in Zambia, Lusaka, Zambia (B.H.C.); Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda (P.M.); University of North Carolina Project, Lilongwe, Malawi (P.K.); Duke University–KCMC Collaboration, Kilimanjaro Christian Medical Centre, Moshi, Tanzania (W.S.); Pharmaceutical AffairsBranch (L.P.) and the Henry Jackson Foundation (P.J.-P.), Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Johns Hopkins University School of Medicine, Baltimore (S.H.E.); International Center for AIDS Care and Treatment Programs, Columbia University Mailman School of Public Health, New York (E.J.A.); Social and Scientific Systems,Silver Spring, MD (E.P.); the Pediatric, Adolescent and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD (L.M.M.); and Frontier Science and Technology Research Foundation, Amherst, NY (L.M.). Address reprint requests to Dr. Palumbo at the Departments of Medicine and Pediatrics, Dartmouth MedicalSchool, Borwell C330W, 1 Medical Center Dr., Lebanon, NH 03765, or at paul.e.palumbo@dartmouth .edu. N Engl J Med 2010;363:1510-20.
Copyright © 2010 Massachusetts Medical Society.
A bs t r ac t
Single-dose nevirapine is the cornerstone of the regimen for prevention of motherto-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapinefrequently 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.
We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6to 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 ofthe data and safety monitoring board.
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...
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