{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:12:34Z","timestamp":1790471554950,"version":"4.1.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK112254"],"award-info":[{"award-number":["R01DK112254"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["1DP1DA037979091"],"award-info":[{"award-number":["1DP1DA037979091"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01Al138718-02"],"award-info":[{"award-number":["5R01Al138718-02"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R0101AI138718"],"award-info":[{"award-number":["R0101AI138718"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Miami Women\u2019s Interagency HIV Infection Study","award":["U01AI103397"],"award-info":[{"award-number":["U01AI103397"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates <jats:italic>ex vivo<\/jats:italic>. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS\/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-<jats:italic>Lactobacillus<\/jats:italic> bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing <jats:italic>Lactobacillus<\/jats:italic> or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1<jats:sub>LAI<\/jats:sub> virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009024","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T18:30:10Z","timestamp":1607020210000},"page":"e1009024","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism"],"prefix":"10.1371","volume":"16","author":[{"given":"Ryan K.","family":"Cheu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-8320","authenticated-orcid":true,"given":"Andrew T.","family":"Gustin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-2178","authenticated-orcid":true,"given":"Christina","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6123-536X","authenticated-orcid":true,"given":"Luca","family":"Schifanella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0090-6465","authenticated-orcid":true,"given":"Charlene J.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-3567","authenticated-orcid":true,"given":"Avie","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7109-6076","authenticated-orcid":true,"given":"Casey","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8543-2061","authenticated-orcid":true,"given":"Violeta J.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-5390","authenticated-orcid":true,"given":"Margaret","family":"Fischl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Burgener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-7461","authenticated-orcid":true,"given":"Kelly B.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-0145","authenticated-orcid":true,"given":"Maria L.","family":"Alcaide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichole R.","family":"Klatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"issue":"8","key":"ppat.1009024.ref001","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1056\/NEJMoa0905848","article-title":"Timing of initiation of antiretroviral drugs during tuberculosis therapy","volume":"362","author":"SS Abdool Karim","year":"2010","journal-title":"New England Journal of Medicine"},{"key":"ppat.1009024.ref002","unstructured":"amfAR. Statistics: Women and HIV\/AIDS2017. Available from: http:\/\/www.amfar.org\/about-hiv-and-aids\/facts-and-stats\/statistics\u2014women-and-hiv-aids\/."},{"issue":"151","key":"ppat.1009024.ref003","doi-asserted-by":"crossref","first-page":"151ra25","DOI":"10.1126\/scitranslmed.3004006","article-title":"Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men","volume":"4","author":"PL Anderson","year":"2012","journal-title":"Science translational medicine"},{"issue":"6341","key":"ppat.1009024.ref004","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1126\/science.aai9383","article-title":"Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women","volume":"356","author":"NR Klatt","year":"2017","journal-title":"Science"},{"issue":"3","key":"ppat.1009024.ref005","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/QAD.0b013e32834ed7f0","article-title":"Bacterial vaginosis, HIV serostatus and T-cell subset distribution in a cohort of East 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