Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women

Nichole R. Klatt, Ryan Cheu, Kenzie Birse, Alexander S. Zevin, Michelle Perner, Laura Noël-Romas, Anneke Grobler, Garrett Westmacott, Irene Y. Xie, Jennifer Butler, Leila Mansoor, Lyle R. McKinnon, Jo Ann S. Passmore, Quarraisha Abdool Karim, Salim S.Abdool Karim, Adam D. Burgener

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154 Scopus citations

Abstract

Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. We investigated whether vaginal microbiota modulated tenofovir gel microbicide efficacy 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 vaginalis predominated with other anaerobic bacteria (40.8%)-were identified in 688 women profiled. 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. 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. This study provides evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism.

Original languageEnglish (US)
Pages (from-to)938-945
Number of pages8
JournalScience
Volume356
Issue number6341
DOIs
StatePublished - Jun 2 2017
Externally publishedYes

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    Klatt, N. R., Cheu, R., Birse, K., Zevin, A. S., Perner, M., Noël-Romas, L., Grobler, A., Westmacott, G., Xie, I. Y., Butler, J., Mansoor, L., McKinnon, L. R., Passmore, J. A. S., Karim, Q. A., Karim, S. S. A., & Burgener, A. D. (2017). Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science, 356(6341), 938-945. https://doi.org/10.1126/science.aai9383