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

doi:10.1126/science.aai9383

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

Research output: Contribution to journal › Article › peer-review

296 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 language	English (US)
Pages (from-to)	938-945
Number of pages	8
Journal	Science (New York, N.Y.)
Volume	356
Issue number	6341
DOIs	https://doi.org/10.1126/science.aai9383
State	Published - Jun 2 2017
Externally published	Yes

Bibliographical note

Keywords

Adult
Antiviral Agents/metabolism
Bacteria/genetics
Biodiversity
Female
Gardnerella/metabolism
HIV Infections/microbiology
Humans
Lactobacillus/metabolism
Mass Spectrometry
Microbiota/genetics
Proteome
RNA, Ribosomal, 16S/genetics
South Africa
Tenofovir/analysis
Vagina/microbiology

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., Abdool Karim, Q., Abdool Karim, S. S., & Burgener, A. D. (2017). Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science (New York, N.Y.), 356(6341), 938-945. https://doi.org/10.1126/science.aai9383

Klatt, NR, Cheu, R, Birse, K, Zevin, AS, Perner, M, Noël-Romas, L, Grobler, A, Westmacott, G, Xie, IY, Butler, J, Mansoor, L, McKinnon, LR, Passmore, J-AS, Abdool Karim, Q, Abdool Karim, SS & Burgener, AD 2017, 'Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women', Science (New York, N.Y.), vol. 356, no. 6341, pp. 938-945. https://doi.org/10.1126/science.aai9383

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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.",

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AU - Perner, Michelle

AU - Noël-Romas, Laura

AU - Grobler, Anneke

AU - Westmacott, Garrett

AU - Xie, Irene Y

AU - Butler, Jennifer

AU - Mansoor, Leila

AU - McKinnon, Lyle R

AU - Passmore, Jo-Ann S

AU - Abdool Karim, Quarraisha

AU - Abdool Karim, Salim S

AU - Burgener, Adam D

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N2 - 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.

AB - 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.

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KW - Antiviral Agents/metabolism

KW - Bacteria/genetics

KW - Biodiversity

KW - Female

KW - Gardnerella/metabolism

KW - HIV Infections/microbiology

KW - Humans

KW - Lactobacillus/metabolism

KW - Mass Spectrometry

KW - Microbiota/genetics

KW - Proteome

KW - RNA, Ribosomal, 16S/genetics

KW - South Africa

KW - Tenofovir/analysis

KW - Vagina/microbiology

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JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6341

ER -

Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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