Background: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. Methods: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. Findings: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). Interpretation: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint - risk of HIV transmission at 6 months - suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. Funding: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.
Bibliographical noteFunding Information:
This study was supported by grants from US National Institutes of Health, the US National Institute of Allergy and Infectious Diseases (R01AI45462, R01AI3857601A, R01AI34235), and the NIH-Fogarty International Center NIH Program of International Training Grants in Epidemiology Related to AIDS (D43-TW0000). The SWEN Study Team express their great appreciation to all of the participating mothers and their infants in Ethiopia, India, and Uganda. We also thank the community advisory boards, as well as the clinicians and staff of the following institutions that were critical to the success of this study and/or who provided clinical care for the study participants: The BJ Medical College/Sassoon General Hospital (BJMC/SGH), Pune, India, The Pune Municipal Corporation (PMC), the Pimpri-Chinchwad Municipal Corporation (PCMC), the National AIDS Research Institute (NARI), Pune, the National AIDS Control Organization (NACO), New Delhi, the Indian Council of Medical Research (ICMR), New Delhi, Addis Ababa University Faculty of Medicine (AAU), Makerere University-Johns Hopkins Research Collaboration (MUJHU) Kampala, Mulago Hospital (MH) Kampala, Makerere University School of Medicine (MUSOM). We also thank Lynne Mofenson, Usha Sharma, and Lydia Soto-Torres for their support, advice, and guidance for this study. The views expressed in this manuscript do not necessarily represent those of the US NIH, BJMC/SGH, PMC, PCMC, NARI, NACO, ICMR, AAU, MUJHU, MH, or MUSOM.