Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota

a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study

Partners PrEP Study Team

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. Methods We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0–3 indicated healthy microbiota, 4–6 intermediate, and 7–10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota. Findings Of 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55% [95% CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72% [95% CI −66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50% [95% CI 5·98 to 91·95]; pinteraction=0·871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68·62% vs 76·72%; pinteraction=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; pinteraction=0·86). Interpretation Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis. Funding Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

Original languageEnglish (US)
Pages (from-to)e449-e456
JournalThe Lancet HIV
Volume4
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Microbiota
Placebos
HIV
Bacterial Vaginosis
Tenofovir
Bacteroides
Lactobacillus
Pre-Exposure Prophylaxis
Incidence
National Institute of Allergy and Infectious Diseases (U.S.)
National Institute of Child Health and Human Development (U.S.)
Dysbiosis
Gardnerella vaginalis
Uganda
Kenya
Microscopy

ASJC Scopus subject areas

  • Epidemiology
  • Immunology
  • Infectious Diseases
  • Virology

Cite this

@article{e137f5246a4f4709b8e8a5a02312106e,
title = "Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study",
abstract = "Background Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. Methods We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0–3 indicated healthy microbiota, 4–6 intermediate, and 7–10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota. Findings Of 1470 women (median age 33 years), 357 (24{\%}) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55{\%} [95{\%} CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72{\%} [95{\%} CI −66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50{\%} [95{\%} CI 5·98 to 91·95]; pinteraction=0·871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68·62{\%} vs 76·72{\%}; pinteraction=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48{\%} vs 74·08{\%}; pinteraction=0·86). Interpretation Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis. Funding Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.",
author = "{Partners PrEP Study Team} and Renee Heffron and McClelland, {R. Scott} and Balkus, {Jennifer E.} and Connie Celum and Cohen, {Craig R.} and Nelly Mugo and Elizabeth Bukusi and Deborah Donnell and Jairam Lingappa and James Kiarie and Tina Fiedler and Matthew Munch and Fredricks, {David N.} and Baeten, {Jared M.} and Connie Celum and Baeten, {Jared M.} and Deborah Donnell and Coombs, {Robert W.} and Kenneth Fife and Hendrix, {Craig W.} and Jairam Lingappa and McElrath, {M. Juliana} and Kenneth Fife and Edwin Were and Elioda Tumwesigye and Patrick Ndase and Elly Katabira and Elly Katabira and Allan Ronald and Elizabeth Bukusi and Craig Cohen and Jonathan Wangisi and James Campbell and Jordan Tappero and James Kiarie and Carey Farquhar and Grace John-Stewart and Mugo, {Nelly Rwamba}",
year = "2017",
month = "10",
day = "1",
doi = "10.1016/S2352-3018(17)30110-8",
language = "English (US)",
volume = "4",
pages = "e449--e456",
journal = "The Lancet HIV",
issn = "2352-3018",
publisher = "Elsevier Limited",
number = "10",

}

TY - JOUR

T1 - Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota

T2 - a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study

AU - Partners PrEP Study Team

AU - Heffron, Renee

AU - McClelland, R. Scott

AU - Balkus, Jennifer E.

AU - Celum, Connie

AU - Cohen, Craig R.

AU - Mugo, Nelly

AU - Bukusi, Elizabeth

AU - Donnell, Deborah

AU - Lingappa, Jairam

AU - Kiarie, James

AU - Fiedler, Tina

AU - Munch, Matthew

AU - Fredricks, David N.

AU - Baeten, Jared M.

AU - Celum, Connie

AU - Baeten, Jared M.

AU - Donnell, Deborah

AU - Coombs, Robert W.

AU - Fife, Kenneth

AU - Hendrix, Craig W.

AU - Lingappa, Jairam

AU - McElrath, M. Juliana

AU - Fife, Kenneth

AU - Were, Edwin

AU - Tumwesigye, Elioda

AU - Ndase, Patrick

AU - Katabira, Elly

AU - Katabira, Elly

AU - Ronald, Allan

AU - Bukusi, Elizabeth

AU - Cohen, Craig

AU - Wangisi, Jonathan

AU - Campbell, James

AU - Tappero, Jordan

AU - Kiarie, James

AU - Farquhar, Carey

AU - John-Stewart, Grace

AU - Mugo, Nelly Rwamba

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. Methods We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0–3 indicated healthy microbiota, 4–6 intermediate, and 7–10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota. Findings Of 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55% [95% CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72% [95% CI −66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50% [95% CI 5·98 to 91·95]; pinteraction=0·871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68·62% vs 76·72%; pinteraction=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; pinteraction=0·86). Interpretation Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis. Funding Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

AB - Background Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. Methods We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0–3 indicated healthy microbiota, 4–6 intermediate, and 7–10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota. Findings Of 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55% [95% CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72% [95% CI −66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50% [95% CI 5·98 to 91·95]; pinteraction=0·871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68·62% vs 76·72%; pinteraction=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; pinteraction=0·86). Interpretation Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis. Funding Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

UR - http://www.scopus.com/inward/record.url?scp=85024889467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024889467&partnerID=8YFLogxK

U2 - 10.1016/S2352-3018(17)30110-8

DO - 10.1016/S2352-3018(17)30110-8

M3 - Article

VL - 4

SP - e449-e456

JO - The Lancet HIV

JF - The Lancet HIV

SN - 2352-3018

IS - 10

ER -