Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women

Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. We investigated whether vaginal microbiota modulated tenofovirgel microbicideefficacy in the CAPRISA (Centre for the AIDS Program of Research in South Africa) 004 trial. Two major vaginal bacterial community types—one dominated by Lactobacillus(59.2%) and the other where Gardnerella vaginalispredominated with other anaerobic bacteria (40.8%)—were identified in 688 women profiled. Tenofovirreduced HIV incidence by 61% ( P = 0.013) in Lactobacillus- dominant women but only 18% ( P = 0.644) in women with non- Lactobacillusbacteria, a threefold difference in efficacy. Detectible mucosal tenofovirwas lower in non- Lactobacilluswomen, negatively correlating with G. vaginalis and other anaerobic bacteria, which depleted tenofovirby metabolism more rapidly than target cells convert to pharmacologically active drug. This study provides evidence linking vaginal bacteria to microbicideefficacy through tenofovirdepletion via bacterial metabolism.