Mary Glenn Fowler1, Hoosen Coovadia, Casey M Herron, Yvonne Maldonado, Tsungai Chipato, Dhayendre Moodley, Philippa Musoke, Jim Aizire, Karim Manji, Lynda Stranix-Chibanda, Wafaie Fawzi, Vani Chetty, Lindiwe Msweli, Rodrick Kisenge, Elizabeth Brown, Anthony Mwatha, Susan H Eshleman, Paul Richardson, Melissa Allen, Kathleen George, Philip Andrew, Sheryl Zwerski, Lynne M Mofenson, J Brooks Jackson. 1. *Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; †Maternal Adolescent and Child Health, University of the Witwatersrand, South Africa; ‡Fred Hutchinson Cancer Research Center, Seattle, WA; §Department of Pediatrics, Stanford University School of Medicine, Stanford, CA; ‖Department of Obstetrics and Gynecology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe; ¶Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa; #Makerere University, Johns Hopkins University, Research Collaboration, Kampala, Uganda; **Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; ††Department of Pediatrics, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe; ‡‡Department of Global Health and Population, Harvard University School of Public Health, Boston, MA; §§Family Health International, Research Triangle Park, NC; ‖‖Division of HIV/AIDS, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD; and ¶¶Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.
Abstract
BACKGROUND: HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. METHODS: Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates. RESULTS: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. CONCLUSIONS: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.
RCT Entities:
BACKGROUND: HPTN 046 compared the efficacy and safety of infantnevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. METHODS: Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infantHIV infection, HIV infection/or death, and mortality rates. RESULTS: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. CONCLUSIONS: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.
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