Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women
Research by a Mucosal Immunology research collaboration between CAPRISA’s mucosal immunology team in Durban and scientists from the USA and Canada was published in Science this week. The study provides new evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism.
Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. Although variability in the levels of adherence has been shown to be a major contributing factor for the diverse trial outcomes in women, little is known about what biological factors may also contribute to the variability in these results.
This study, which included biological samples from 688 HIV-negative women from the CAPRISA 004 trial, used a metaproteomic approach to assess whether vaginal bacteria modulate the efficacy of the topical microbicide tenofovir in preventing
Two major vaginal bacterial community types were identified; one dominated by Lactobacillus (59.2%), and the other where Gardnerella vaginalis predominated with other anaerobic bacteria (40.8%).
Tenofovir reduced HIV incidence by 61% (P=0.013) in Lactobacillus-dominant women but only 18% (P=0.644) in women with non-Lactobacillus bacteria - a threefold difference in efficacy (Figure below).
An in vitro culture system was used to assess potential biodegradation of tenofovir by the major bacterial species present in this cohort. The results show that detectible
mucosal tenofovir was lower in non-Lactobacillus women, negatively correlating with G. vaginalis and other anaerobic bacteria, which depleted tenofovir by metabolism more rapidly than target cells convert to pharmacologically active drug.
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