Twelve-month follow-up of Six Week Extended Dose Nevirapine randomized controlled trials: differential impact of extended-dose nevirapine on mother-to-child transmission and infant death by maternal CD4 cell count

We previously reported combined analysis of 6-week and 6-month endpoints of three randomized controlled trials [Six Week Extended Dose Nevirapine (SWEN) trials] that compared extended-dose nevirapine through 6 weeks of age to single-dose nevirapine to prevent HIV transmission via breastfeeding and mortality. We now present endpoints through 12 months of age. Infants in Ethiopia, India, and Uganda born to HIV-infected women who chose to breastfeed were randomized to receive single-dose or extended-dose nevirapine. HIV transmission, mortality, HIV transmission or death. Primary analysis included 987 and 903 infants in the single-dose and the extended-dose arms, respectively. HIV transmission was 8.9% in the extended-dose group compared to 10.4% in the single-dose group, but the difference was not significant [risk ratio: 0.87, 95% confidence interval (CI): 0.65-1.15]. Cumulative mortality at 12 months was half in the extended-dose group compared to the single-dose group (risk ratio: 0.53, 95% CI: 0.32-0.85). The impact of extended-dose nevirapine was highest in infants of mothers with CD4 cell count more than 350 cells/μl. Risk ratios for death (risk ratio: 0.38, 95% CI: 0.17-0.84) and HIV transmission or death (risk ratio: 0.54, 95% CI: 0.35-0.85) were statistically significant for the CD4 cell counts more than 350 cells/μl category, whereas none of the risk ratios were significant for the CD4 cell counts 200 cells/μl or less and CD4 cell counts 201-350 cells/μl categories. For populations with limited access to HAART, our results provide evidence for the use of extended-dose regimens to prevent infant deaths and increase HIV-free survival in infants of HIV-infected breastfeeding women, particularly for infants of women with CD4 cell counts more than 350 cells/μl.