Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. This phase III double-blind, placebo-controlled study (HPTN 046), sponsored by the US National Institutes of Health, evaluated incremental safety and efficacy of extension of such prophylaxis to 6 months.

The study involved 1527 breastfeeding infants born to mothers with HIV in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, those without HIV infection were randomised to receive extended nevirapine prophylaxis (n= 762) or placebo (n= 765) until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV infection in infants at 6 months and safety endpoints were adverse reactions in both groups.

The following findings were reported:

• Five infants had HIV infection at randomisation and were excluded from the primary analyses.

• 1.1% of infants on extended nevirapine developed HIV between 6 weeks and 6 months compared with 2.4% of controls (difference 1.3%), equating to a 54% reduction in transmission (p=0.049).

• Mortality (1.2% for nevirapine vs. 1.1% for placebo; p=0.81) and combined HIV infection and mortality rates (2.3% vs. 3.2%; p=0.27) did not differ between groups at 6 months.

• 125 (16%) of 758 infants on extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups.

The researchers conclude that after 6 weeks of treatment with once-daily nevirapine, continued use to age 6 months in uninfected infants of breastfeeding mothers with HIV, is safe, and results in a greater than 50% reduction in mother-to-child transmission from breastfeeding compared with placebo. They note that once prophylaxis ends, transmission risk returns at rates much the same as that reported without prophylaxis. They add, that these results provide further evidence for the safety and efficacy of infant nevirapine prophylaxis for 6 months of exclusive breastfeeding, as is recommended by the WHO, as well as a proof of principle for the WHO recommendations to continue infant antiretroviral prophylaxis throughout the period of breastfeeding, whether it lasts 6 months or longer.