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; Partners PrEP Study Team

doi:10.1016/S2352-3018(17)30110-8

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, Partners PrEP Study Team

School of Medicine

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

31 Scopus citations

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]; p_interaction=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%; p_interaction=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; p_interaction=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 language	English (US)
Pages (from-to)	e449-e456
Journal	The Lancet HIV
Volume	4
Issue number	10
DOIs	https://doi.org/10.1016/S2352-3018(17)30110-8
State	Published - Jan 1 2017

ASJC Scopus subject areas

Epidemiology
Immunology
Infectious Diseases
Virology

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10.1016/S2352-3018(17)30110-8

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@article{3d7a75a5492a4e18b907fc3121eb9592,

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 {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 Coombs, {Robert W.} and Lisa Frenkel and Hendrix, {Craig W.} and McElrath, {M. Juliana} and Kenneth Fife and Edwin Were and Elioda Tumwesigye and Patrick Ndase and Elly Katabira and Allan Ronald and Jonathan Wangisi and James Campbell and Jordan Tappero and Carey Farquhar and Grace John-Stewart and Mugo, {Nelly Rwamba}",

note = "Funding Information: We found no evidence that the protective benefit of daily oral PrEP was reduced in east African women with Gram-stain evidence of bacterial vaginosis or vaginal dysbiosis compared with those with healthy vaginal microbiota. Bacterial vaginosis was common: 24% of participants had bacterial vaginosis by Gram-stain criteria at baseline, and 37% had G vaginalis or Bacteroides spp morphotypes. Gram-stain results were consistent with quantitative PCR findings in a subset of women, showing that women tended to sort into groups with greater presence of either Lactobacillus spp or Gardnerella spp. We noted a non-significant association between abnormal vaginal microbiota and increased risk of HIV acquisition, a finding similar to those in other studies. 23 Our data are reassuring that oral PrEP is efficacious for women with abnormal vaginal microbiota. In CAPRISA 004, 5 a randomised trial of 1% tenofovir gel for HIV prevention among high-risk South African women, primary results showed that the gel had moderate protective benefits (39% efficacy [95% CI 6–60). However, a secondary analysis of CAPRISA 004 data suggests that vaginal dysbiosis, as diagnosed by metaproteomic methods, could modify the protective effect of the gel: women with non- Lactobacillus -dominant microbiota received no protective benefits, whereas those with Lactobacillus -dominant microbiota did. 16 We used a different method to assess vaginal dysbiosis (Gram staining, supported by quantitative PCR testing in a subset), but the approaches used in the CAPRISA 004 analysis and in our testing would probably have classified women's dysbiosis status similarly. Our results for oral tenofovir-based PrEP do not show the same striking efficacy differences that were reported in CAPRISA 004 with topically applied PrEP. The metabolic processes for oral PrEP and tenofovir gel are different. The active agents in oral PrEP are systemically distributed to be present in mucosal surfaces and vaginal tissues. 24,25 By contrast, 1% tenofovir gel is at greatest concentrations in the vagina and penetrates only minimally beyond the mucosa and into plasma. 26,27 Thus the pathways that oral and topical formulations take to reach HIV target cells and prevent HIV acquisition are distinct. Because oral PrEP is absorbed and metabolised systemically, modulation of efficacy by a local mediator, such as bacterial vaginosis or vaginal dysbiosis, is probably less likely. Adherence to the daily oral PrEP regimen was very high in this cohort, with previous analyses suggesting that more than 80% of participants had plasma concentrations consistent with daily use. 1 Work to understand the pharmacokinetics and pharmacodynamics of daily-use tenofovir-based PrEP has suggested that missing doses might be less of an issue in men who have sex with men than in heterosexual women, because tenofovir is metabolised differently in cervicovaginal and rectal tissue. 9 Further research is needed to understand fully how the genital microbiome could modify this metabolism and the necessary adherence level for optimal HIV protection benefits from oral PrEP and other drugs in development. In our primary analysis of PrEP efficacy among women with Nugent scores of 7–10 compared with those with Nugent scores of 0–3, assessed in a time-dependent fashion, the degree of protection afforded by PrEP did not differ significantly between groups. However, our statistical power to detect an interaction was limited because our trial was not powered for this subgroup analysis. In other comparisons of markers of vaginal dysbiosis, we had limited power to observe statistical differences in the degree of protection by PrEP. Nonetheless, the HIV incidence in women in the PrEP group was substantially less than that in women in the placebo group in all subgroups, and the HR estimates for protection from PrEP were significant for many subgroups. We used microscopy to determine Nugent scores and the presence of bacterial vaginosis. This method provides information about the abundance of bacterial morphotypes but does not identify individual bacterial species. 20 In a subset of participants we did quantitative PCR, and detected a strong association between high Nugent scores and the concentration of G vaginalis , consistent with the findings of previous studies. 21 The CAPRISA analysis identified G vaginalis as an important species that could disrupt HIV protection from tenofovir 1% gel, prompting our analysis with the Gardnerella spp or Bacteroides spp component of the Nugent score. However, the score aggregates Gardnerella spp and Bacteroides spp morphotypes, masking the relative presence of each, which limits our ability to determine which morphotypes are more common. Further work to characterise the microbiome and estimate oral PrEP efficacy in the presence of different vaginal microbiome types (eg lactobacilli-dominated or anaerobic dysbiosis) are important to support or to refute our findings and to increase understanding of how the microbiome interacts with topical and systemically delivered PrEP. Specific bacteria are postulated to increase HIV risk through inflammatory mechanisms, including Prevotella bivia, Gemella asaccharolytica, Megasphaera, Mycoplasma hominis, Leptotrichia spp, Sneathia spp, and Eggerthella spp type 1, 13,28,29 and the potential role that these bacteria have in disruption of oral PrEP efficacy is unknown. Another limitation of our work is that we measured Nugent scores yearly, and some women frequently transition between vaginal microbiota states. More frequent measurement would minimise misclassification, and longitudinal pharmacokinetic studies among smaller samples would provide key metabolic data. PrEP is being rolled out in sub-Saharan Africa to high-risk groups, including young women in areas with particularly high HIV burden, in whom bacterial vaginosis and abnormal vaginal microbiota are particularly common. Our results suggest that, in the setting of high adherence to PrEP, women with vaginal dysbiosis receive the same high level of protection as women with healthy microbiota. Integration of PrEP delivery with other services, such as testing for sexually transmitted infections and reproductive health care, is the ideal option as PrEP delivery programmes are developed to scale. Our data are reassuring that testing for bacterial vaginosis or any marker of vaginal dysbiosis is unnecessary before oral PrEP delivery. They also suggest that treatment of bacterial vaginosis is unnecessary to ensure protective benefits from oral PrEP. As implementation continues, expansion of delivery through models that make PrEP available to women at high risk and maximise adherence should ensure the greatest effect on reducing HIV incidence. Contributors RH and JMB conceived the study. RH did the statistical analyses and wrote the first draft of the Article. RSM and DNF oversaw laboratory technicians who did the analyses of vaginal dysbiosis. All authors contributed critical revisions to the analysis and interpretation, and reviewed the final Article. Declaration of interests RSM has received research funding from Hologic , paid as a grant to the University of Washington. All other authors declare no competing interests. Acknowledgments The Partners PrEP Study was funded by the Bill & Melinda Gates Foundation ( OPP47674 ). Our work was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( R00-HD076679 and P01-HD64915 ) and the National Institute of Allergy and Infectious Diseases ( P30-AI027757 and R01-AI096968 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders or the institutions with which they are affiliated. We thank the couples who participated in this study and the teams at the study sites for work on data collection and management and the director of the Kenya Medical Research Institute. Partners PrEP Study Team Connie Celum (principal investigator, protocol co-chair), Jared M Baeten (medical director, protocol co-chair), Deborah Donnell (protocol statistician), Robert W Coombs, Lisa Frenkel, Craig W Hendrix, Jairam Lingappa, M Juliana McElrath, Kenneth Fife, Edwin Were, Elioda Tumwesigye, Patrick Ndase, Elly Katabira, Elly Katabira, Allan Ronald, Elizabeth Bukusi, Craig Cohen, Jonathan Wangisi, James Campbell, Jordan Tappero, James Kiarie, Carey Farquhar, Grace John-Stewart, Nelly Rwamba Mugo. Funding Information: The Partners PrEP Study was funded by the Bill & Melinda Gates Foundation (OPP47674). Our work was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00-HD076679 and P01-HD64915) and the National Institute of Allergy and Infectious Diseases (P30-AI027757 and R01-AI096968). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders or the institutions with which they are affiliated. We thank the couples who participated in this study and the teams at the study sites for work on data collection and management and the director of the Kenya Medical Research Institute. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

month = jan,

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 - Coombs, Robert W.

AU - Frenkel, Lisa

AU - Hendrix, Craig W.

AU - McElrath, M. Juliana

AU - Fife, Kenneth

AU - Were, Edwin

AU - Tumwesigye, Elioda

AU - Ndase, Patrick

AU - Katabira, Elly

AU - Ronald, Allan

AU - Wangisi, Jonathan

AU - Campbell, James

AU - Tappero, Jordan

AU - Farquhar, Carey

AU - John-Stewart, Grace

AU - Mugo, Nelly Rwamba

N1 - Funding Information: We found no evidence that the protective benefit of daily oral PrEP was reduced in east African women with Gram-stain evidence of bacterial vaginosis or vaginal dysbiosis compared with those with healthy vaginal microbiota. Bacterial vaginosis was common: 24% of participants had bacterial vaginosis by Gram-stain criteria at baseline, and 37% had G vaginalis or Bacteroides spp morphotypes. Gram-stain results were consistent with quantitative PCR findings in a subset of women, showing that women tended to sort into groups with greater presence of either Lactobacillus spp or Gardnerella spp. We noted a non-significant association between abnormal vaginal microbiota and increased risk of HIV acquisition, a finding similar to those in other studies. 23 Our data are reassuring that oral PrEP is efficacious for women with abnormal vaginal microbiota. In CAPRISA 004, 5 a randomised trial of 1% tenofovir gel for HIV prevention among high-risk South African women, primary results showed that the gel had moderate protective benefits (39% efficacy [95% CI 6–60). However, a secondary analysis of CAPRISA 004 data suggests that vaginal dysbiosis, as diagnosed by metaproteomic methods, could modify the protective effect of the gel: women with non- Lactobacillus -dominant microbiota received no protective benefits, whereas those with Lactobacillus -dominant microbiota did. 16 We used a different method to assess vaginal dysbiosis (Gram staining, supported by quantitative PCR testing in a subset), but the approaches used in the CAPRISA 004 analysis and in our testing would probably have classified women's dysbiosis status similarly. Our results for oral tenofovir-based PrEP do not show the same striking efficacy differences that were reported in CAPRISA 004 with topically applied PrEP. The metabolic processes for oral PrEP and tenofovir gel are different. The active agents in oral PrEP are systemically distributed to be present in mucosal surfaces and vaginal tissues. 24,25 By contrast, 1% tenofovir gel is at greatest concentrations in the vagina and penetrates only minimally beyond the mucosa and into plasma. 26,27 Thus the pathways that oral and topical formulations take to reach HIV target cells and prevent HIV acquisition are distinct. Because oral PrEP is absorbed and metabolised systemically, modulation of efficacy by a local mediator, such as bacterial vaginosis or vaginal dysbiosis, is probably less likely. Adherence to the daily oral PrEP regimen was very high in this cohort, with previous analyses suggesting that more than 80% of participants had plasma concentrations consistent with daily use. 1 Work to understand the pharmacokinetics and pharmacodynamics of daily-use tenofovir-based PrEP has suggested that missing doses might be less of an issue in men who have sex with men than in heterosexual women, because tenofovir is metabolised differently in cervicovaginal and rectal tissue. 9 Further research is needed to understand fully how the genital microbiome could modify this metabolism and the necessary adherence level for optimal HIV protection benefits from oral PrEP and other drugs in development. In our primary analysis of PrEP efficacy among women with Nugent scores of 7–10 compared with those with Nugent scores of 0–3, assessed in a time-dependent fashion, the degree of protection afforded by PrEP did not differ significantly between groups. However, our statistical power to detect an interaction was limited because our trial was not powered for this subgroup analysis. In other comparisons of markers of vaginal dysbiosis, we had limited power to observe statistical differences in the degree of protection by PrEP. Nonetheless, the HIV incidence in women in the PrEP group was substantially less than that in women in the placebo group in all subgroups, and the HR estimates for protection from PrEP were significant for many subgroups. We used microscopy to determine Nugent scores and the presence of bacterial vaginosis. This method provides information about the abundance of bacterial morphotypes but does not identify individual bacterial species. 20 In a subset of participants we did quantitative PCR, and detected a strong association between high Nugent scores and the concentration of G vaginalis , consistent with the findings of previous studies. 21 The CAPRISA analysis identified G vaginalis as an important species that could disrupt HIV protection from tenofovir 1% gel, prompting our analysis with the Gardnerella spp or Bacteroides spp component of the Nugent score. However, the score aggregates Gardnerella spp and Bacteroides spp morphotypes, masking the relative presence of each, which limits our ability to determine which morphotypes are more common. Further work to characterise the microbiome and estimate oral PrEP efficacy in the presence of different vaginal microbiome types (eg lactobacilli-dominated or anaerobic dysbiosis) are important to support or to refute our findings and to increase understanding of how the microbiome interacts with topical and systemically delivered PrEP. Specific bacteria are postulated to increase HIV risk through inflammatory mechanisms, including Prevotella bivia, Gemella asaccharolytica, Megasphaera, Mycoplasma hominis, Leptotrichia spp, Sneathia spp, and Eggerthella spp type 1, 13,28,29 and the potential role that these bacteria have in disruption of oral PrEP efficacy is unknown. Another limitation of our work is that we measured Nugent scores yearly, and some women frequently transition between vaginal microbiota states. More frequent measurement would minimise misclassification, and longitudinal pharmacokinetic studies among smaller samples would provide key metabolic data. PrEP is being rolled out in sub-Saharan Africa to high-risk groups, including young women in areas with particularly high HIV burden, in whom bacterial vaginosis and abnormal vaginal microbiota are particularly common. Our results suggest that, in the setting of high adherence to PrEP, women with vaginal dysbiosis receive the same high level of protection as women with healthy microbiota. Integration of PrEP delivery with other services, such as testing for sexually transmitted infections and reproductive health care, is the ideal option as PrEP delivery programmes are developed to scale. Our data are reassuring that testing for bacterial vaginosis or any marker of vaginal dysbiosis is unnecessary before oral PrEP delivery. They also suggest that treatment of bacterial vaginosis is unnecessary to ensure protective benefits from oral PrEP. As implementation continues, expansion of delivery through models that make PrEP available to women at high risk and maximise adherence should ensure the greatest effect on reducing HIV incidence. Contributors RH and JMB conceived the study. RH did the statistical analyses and wrote the first draft of the Article. RSM and DNF oversaw laboratory technicians who did the analyses of vaginal dysbiosis. All authors contributed critical revisions to the analysis and interpretation, and reviewed the final Article. Declaration of interests RSM has received research funding from Hologic , paid as a grant to the University of Washington. All other authors declare no competing interests. Acknowledgments The Partners PrEP Study was funded by the Bill & Melinda Gates Foundation ( OPP47674 ). Our work was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( R00-HD076679 and P01-HD64915 ) and the National Institute of Allergy and Infectious Diseases ( P30-AI027757 and R01-AI096968 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders or the institutions with which they are affiliated. We thank the couples who participated in this study and the teams at the study sites for work on data collection and management and the director of the Kenya Medical Research Institute. Partners PrEP Study Team Connie Celum (principal investigator, protocol co-chair), Jared M Baeten (medical director, protocol co-chair), Deborah Donnell (protocol statistician), Robert W Coombs, Lisa Frenkel, Craig W Hendrix, Jairam Lingappa, M Juliana McElrath, Kenneth Fife, Edwin Were, Elioda Tumwesigye, Patrick Ndase, Elly Katabira, Elly Katabira, Allan Ronald, Elizabeth Bukusi, Craig Cohen, Jonathan Wangisi, James Campbell, Jordan Tappero, James Kiarie, Carey Farquhar, Grace John-Stewart, Nelly Rwamba Mugo. Funding Information: The Partners PrEP Study was funded by the Bill & Melinda Gates Foundation (OPP47674). Our work was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00-HD076679 and P01-HD64915) and the National Institute of Allergy and Infectious Diseases (P30-AI027757 and R01-AI096968). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders or the institutions with which they are affiliated. We thank the couples who participated in this study and the teams at the study sites for work on data collection and management and the director of the Kenya Medical Research Institute. Publisher Copyright: © 2017 Elsevier Ltd

PY - 2017/1/1

Y1 - 2017/1/1

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.

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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

C2 - 28732773

AN - SCOPUS:85024889467

SN - 2352-3018

VL - 4

SP - e449-e456

JO - The Lancet HIV

JF - The Lancet HIV

IS - 10

ER -

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

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