A randomized, double-blind, placebo-controlled trial of combined nevirapine and zidovudine compared with nevirapine alone in the prevention of perinatal transmission of HIV in Zimbabwe.

A single dose of nevirapine (sdNVP) administered to both mother and infant can decrease mother-to-child transmission of human immunodeficiency virus (HIV) by 47% compared with ultra-short course zidovudine therapy (usZDV). There is limited data about the benefit of usZDV added to sdNVP to prevent mother-to-child transmission. We performed a double-blind randomized placebo-controlled trial to determine whether usZDV combined with sdNVP improved neonatal outcome compared with sdNVP alone. Mothers were randomized to 1 of 2 treatment groups. Mothers in the usZDV/sdNVP group received a loading dose of zidovudine (600 mg administered orally) and continued to receive 300-mg doses of zidovudine orally every 3 h while in labor and their infants received zidovudine at a dosage of 2 mg per kg of body weight 4 times per day orally for 72 h. Mothers and infants in the sdNVP group received zidovudine placebo dosed in the same manner. All mothers also received nevirapine at a dosage of 200 mg orally while in labor and all infants received nevirapine 2 mg per kg of body weight orally within 72 h of delivery. The study was stopped on the basis of futility because interim data showed that at present trends superiority would not be demonstrated. Results at 6 weeks of age were available for 609 infants. The primary end point of HIV RNA positivity or death occurred in 21.8% of infants in the usZDV/sdNVP arm and 23.6% of the infants in the sdNVP arm. usZDV when added to a standard 2-dose regimen of sdNVP did not demonstrate a clinically important decrease in the combined end point of mother-to-child transmission or infant death. High rates of adverse maternal and infant outcome in both study arms suggest that improved approaches are necessary. (authors)