Phase III double blind placebo-controlled trial of infant periexposure prophylaxis with 3TC to prevent HIV-1 transmission by breastfeeding

Postnatal transmission of HIV-1 through breast milk remains an unsolved problem in many resource-poor settings. In Sub-Saharan Africa, especially in the rural areas, replacement feeding has proven a problematic alternative because of social, cultural, eco nomic and hygienic constraints. Moreover, studies have shown that exclusively or predominantly breastfed infants have a substantially reduced risk of succumbing to common childhood infections such as diarrhoea and pneumonia; diseases that also inflict a s ubstantial nutritional insult. Therefore, strategies to prevent MTCT of HIV-1 that allows for maintenance of BF for an optimal period of time are urgently needed. In observational studies, exclusive breast feeding (EBF) was associated with a reduced risk of HIV-1 transmission as compared to mixed feeding. The PROMISE PEP study is a randomised double-blind placebo-controlled multi-centre trial that will measure the efficacy of prolonged peri-exposure prophylaxis (PEP) with lamivudine (3TC) to prevent HIV- 1-transmission through breast milk and death in children born to HIV-1-infected mothers not eligible for HAART and having benefited from WHO-recommended enhanced perinatal antiretroviral (ARV) regimens. The study will recruit 1900 mother-infant pairs in 4 African countries. This application tries to mobilise Norwegian co-funding for this relatively large study that already has approved funding from EDCTP and ANRS (French national aids research agency). Objectives: See previous heading Main endpoint HIV-1 -free survival until 9 months of age [event: infant death or acquisition of HIV-1 infection in infants (as assessed by PCR), between day 1/ 7 and month 9]. Expected outcome This study will provide a new evidence-based drug regimen to support HIV-1-infecte d women not eligible for HAART to safely breastfeed their babies, thus counteracting the existing contradiction between optimal infant feeding and PMTCT through breast milk