Efficacy and Safety of an Extended Nevirapine Regimen in Infant Children of Breastfeeding Mothers With HIV-1 Infection for Prevention of Postnatal HIV-1 Transmission (HPTN 046): A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Nevirapine prophylaxis until age 6 weeks reduces transmission of HIV-1 via breast milk. This study evaluated the incremental safety and efficacy of infant nevirapine prophylaxis from ages 6 weeks to 6 months.Breastfeeding infants born to mothers with HIV-1 in South Africa, Tanzania, Uganda, or Zimbabwe were recruited within 7 days of birth.In this randomized, double-blind, placebo-controlled trial, all infants received once-daily nevirapine from birth to age 6 weeks. Infants without HIV-1 at 6 weeks were randomly allocated to receive once-daily nevirapine prophylaxis or placebo until age 6 months or breastfeeding cessation, whichever occurred first. Randomization was stratified by recruitment site and maternal antiretroviral treatment status. Kaplan–Meier analyses were used to compare HIV-1 infection at age 6 months and adverse events.Overall, 1527 infants received nevirapine (n = 762) or placebo (n = 765). From 6 weeks to 6 months, HIV-1 developed in 1.1% (95% confidence interval [CI]: 0.35–1.8%) of infants on nevirapine and 2.4% (95% CI: 1.3%–3.6%) of infants on placebo (54% reduction, P = .049). Infants of mothers not on antiretroviral therapy were less likely to develop HIV-1 on nevirapine (1.3%) than placebo (3.4%, P = .027), even among mothers with higher CD4 counts (0.7% vs 2.8%, P = .014). The effects of nevirapine prophylaxis were no longer significant by ages 9 to 12 months, and >95% of infants were no longer breastfed by age 9 months. Mortality at age 6 months (nevirapine, 1.2%; placebo, 1.1%; P = .81) and adverse events did not differ between treatment groups.Once-daily nevirapine prophylaxis reduces mother-to-child HIV-1 transmission via breast milk up to age 6 months, especially if the mother is not taking antiretroviral therapy.Although extended nevirapine prophylaxis reduced mother-to-child HIV-1 transmission in the first 6 months, risk of transmission returned once prophylaxis was stopped and overall infant mortality did not change. Further studies should evaluate the relative safety and efficacy of extending nevirapine prophylaxis beyond age 6 months and the relative benefits of breastfeeding until age 24 months for prevention of infant mortality due to respiratory and diarrheal illnesses versus the continued risk of HIV-1 transmission.