Background:  In many developing countries, breast-feeding reduces the value of antenatal and peri-partum HIV chemoprophylaxis interventions, but formula-feeding is often associated with increased infant morbidity and mortality. Strategies to reduce postnatal HIV transmission and extend HIV-free infant survival are desperately needed.

Methods:  HIV⁺ pregnant women presenting for antenatal care at 4 sites in Botswana were randomized to a partially double blinded, 2x2 factorial clinical trial investigating several perinatal interventions and infant feeding strategies to prevent mother-to-child HIV transmission. We present the first planned final results from the feeding strategy interventions in which all infants received 1 month zidovudine (ZDV) prophylaxis and either formula-feeding (FF) or breast-feeding plus ZDV through 6 months (BF+ZDV). All mothers received antenatal and intra-partum prophylaxis. The primary efficacy endpoints for the feeding interventions were 7-month HIV positivity and 18-month HIV-free survival. Cumulative event rates were estimated from Kaplan-Meier methods.

Results:  Of the 1200 HIV⁺ women randomized, 591 infants assigned to FF and 588 to BF+ZDV were live-born. By 18 months, 86 infants had acquired HIV, 109 died, and 166 either acquired HIV or died. Cumulative overall infant adverse event rates at 7 months were similar, except for higher mortality in the FF arm (7.6% vs 3.7%, p = 0.003); 9.2% in the BF+ZDV arm stopped ZDV for toxicity. The cumulative 7-month HIV positivity rates were 5.6% and 9.1% in the FF and BF+ZDV arms, respectively (95% confidence interval for difference [BF+ZDV – FF], 0.4 to 6.5%, p = 0.04]. The cumulative rates of HIV-free survival at 18 months were 86% and 84% for FF and BF+ZDV arms, respectively (95% CI for difference, –6.0 to 2.5%, p = 0.42). There was some evidence of a quantitative interaction between feeding strategy and perinatal intervention arms, with the FF advantage greater when mothers and infants received single-dose NVP than when they did not.

Conclusions:  This is the first study to compare 2 different types of intervention to prevent postnatal HIV transmission. The BF+ZDV arm had higher HIV infection and lower mortality rates than the FF arm by 7 months and comparable HIV-free survival rates by 18 months. While the application of these results may differ depending on socioeconomic conditions and public health infrastructure, high rates of HIV-free survival through 18 months of age were achieved with both infant feeding strategies.

Keywords: prevention of mother to child transmission of HIV; infant feeding; antiretroviral prophylaxis