Antiretroviral Safe in Reducing HIV-1 Transmission via Breast-Feeding

m Medscape Education Clinical Briefs News Author: Laurie Barclay, MD CME Author: Hien T. Nghiem, MD 01/10/2012 Clinical Context Breast-feeding in sub-Saharan Africa is an important source of nutrition for infants between birth and age 24 months, leading to improved overall survival duration. However, breast-feeding for infants exposed to HIV can account for 30% to 40% of all mother-to-child transmissions. Strategies for prevention of mother-to-child transmission are needed. Guidelines from the World Health Organization recommend extended breast-feeding for infants exposed to HIV-1 until age 12 months, together with antiretroviral prophylaxis for the mother or infant for the duration of breast-feeding. Nevirapine given once daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breast-feeding reduces transmission through this route vs single-dose nevirapine at birth or neonatally. The aim of this study by Coovadia and colleagues was to assess the incremental safety and efficacy of extension of such prophylaxis to 6 months. Study Synopsis and Perspective A daily oral dose of nevirapine given to infants up to 6 months of age can safely reduce mother-to-child transmission of HIV-1 via breast-feeding, according to the results of a phase 3, double-blind, randomized, placebo-controlled trial published online December 23 in the Lancet. "Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally," write Professor Hoosen M. Coovadia, MD, from the University of Witwatersrand in Johannesburg and the Nelson Mandela School of Medicine at the University of Kwazulu-Natal in Durban, South Africa, and colleagues. "We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months." Within 7 days of birth, breast-feeding infants born to mothers with HIV-1 in 4 African countries were enrolled and given once-daily nevirapine from birth to 6 weeks. Using a computer-generated permuted block algorithm with random block sizes allowing stratification by site and maternal antiretroviral treatment status, 6-week-old infants without HIV infection were assigned to receive extended nevirapine prophylaxis or placebo either until 6 months or until breast-feeding stopped, whichever came first. Kaplan-Meier analyses allowed between-group comparison of the primary efficacy outcome of HIV-1 infection in infants at 6 months. Adverse reactions were also recorded in both groups as safety endpoints. Of 1527 infants randomly assigned between June 19, 2008, and March 12, 2010, 762 were assigned to receive nevirapine, and 765 to receive placebo. Five of these patients were excluded from the primary analyses because they had HIV-1 infection at randomization. HIV-1 infection occurred between 6 weeks and 6 months in 1.1% (95% confidence interval [CI], 0.3% - 1.8%) of infants who received extended nevirapine, and in 2.4% (95% CI, 1.3% - 3.6%) of those who received placebo. Reduction in transmission associated with extended nevirapine was 54% (difference, 1.3%; 95% CI, 0% - 2.6%; P = .049). At 6 months, both groups had similar mortality rates (1.2% with nevirapine vs 1.1% with placebo; P = .81) and combined HIV infection and mortality rates (2.3% vs 3.2%; P = .27). The treatment groups had no significant differences in frequency of adverse events, serious adverse events (16% vs 15%), and deaths. Limitations of this study include a lack of adjustment for multiple statistical tests, which could increase the risk for false-positive findings. "After 6 weeks of treatment with once-daily nevirapine, continued use of nevirapine to age 6 months in uninfected infants of breastfeeding mothers with HIV-1 is safe, and results in a greater than 50% reduction in mother-to-child transmission from breastfeeding compared with placebo," the study authors write. "No other study has directly assessed the incremental benefit of extension of nevirapine from age 6 weeks until 6 months to establish whether the extended period is more efficacious and whether there are increased safety issues associated with long-term treatment with nevirapine." The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships. Lancet. Published online December 23, 2011. Abstract