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Science. 2017 Jun 2;356(6341):938-945. doi: 10.1126/science.aai9383.

Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women.

Author information

1
Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, WA, USA. adam.burgener@umanitoba.ca klattnr@uw.edu.
2
Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, WA, USA.
3
National HIV and Retrovirology Labs, J.C. Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
4
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
5
Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
6
Mass Spectrometry and Proteomics Core Facility, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
7
Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.
8
Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA.
9
National HIV and Retrovirology Labs, J.C. Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada. adam.burgener@umanitoba.ca klattnr@uw.edu.
10
Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

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.

PMID:
28572388
DOI:
10.1126/science.aai9383
[Indexed for MEDLINE]

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