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

Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada
Clinical Infectious Diseases (Impact Factor: 8.89). 02/2007; 44(1):111-9. DOI: 10.1086/508869
Source: PubMed


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.

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Available from: Michael S Silverman, Nov 18, 2015
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    • "Thirteen trials were terminated earlier than planned. Reasons for early termination included a significant effect of the intervention detected during data monitoring [14]–[18] and no significant effect during data monitoring [19]–[21]. In two of these trials, the results of data monitoring were confirmed in a recently published trial employing the same intervention [20], [21]. "
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    • "In this case, the argument goes, continuing the trial may not be justifiable in terms of time, money, and effort. For example, Thistle et al. recently truncated their investigation of whether an ultrashort course of zidovudine therapy combined with a single dose of nevirapine would improve neonatal outcome compared with nevirapine alone [2]. Third, new external information may arise during the conduct of the study that either convincingly answers the primary study question or that raises serious safety issues. "
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