{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:57:23Z","timestamp":1791053843669,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The vaginal microbiome plays a complex role in tenofovir's mucosal pharmacology. While the relative contribution of systemic versus local concentrations to PrEP PK\/PD is an ongoing debate, the development of effective HIV prevention requires an understanding of events at the site of transmission. Our objective was to further understand the relationship between tenofovir mucosal pharmacology and non\u2010optimal vaginal microbiota using the ex\u00a0vivo vaginal tissue model. Vaginal and cervical explants were produced from cadaver tissue using a biopsy punch. Explants were incubated with\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Prevotella bivia<\/jats:italic>\n                    <\/jats:styled-content>\n                    (10\n                    <jats:sup>3<\/jats:sup>\n                    \u201310\n                    <jats:sup>5<\/jats:sup>\n                    colony forming units\/ml) with and without tenofovir for 24\u2009h. TFVdp and endogenous adenosine triphosphate (dATP) were quantified using liquid chromatography tandem mass spectroscopy. Explants were then challenged with 10\n                    <jats:sup>6<\/jats:sup>\n                    TCID\n                    <jats:sub>50<\/jats:sub>\n                    the viral concentration where 50% of tissue cultures are infected, of HIV\n                    <jats:sub>JR\u2010CSF<\/jats:sub>\n                    for 3\u2009h. Explants were cultured on gel\u2010foam rafts for 48\u2009h then collected for HIV RNA quantification using RT\u2010qPCR. TFVdp formation in vaginal tissue was approximately 76% lower in anaerobic conditions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.2) compared to aerobic. While dATP concentrations did not significantly differ between any\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Prevotella bivia<\/jats:italic>\n                    <\/jats:styled-content>\n                    concentrations and the\n                    <jats:italic>Prevotella\u2010<\/jats:italic>\n                    free control, TFVdp and TFVdp:dATP ratio in vaginal tissue decreased as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Prevotella bivia<\/jats:italic>\n                    <\/jats:styled-content>\n                    concentrations increased, although not statistically. Unexpectedly, tenofovir efficacy increased as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Prevotella bivia<\/jats:italic>\n                    <\/jats:styled-content>\n                    concentrations increased. The ex\u00a0vivo tissue model was successful in demonstrating the pharmacology of TFVdp is affected by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Prevotella bivia<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Viral replication was also affected by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Prevotella bivia<\/jats:italic>\n                    <\/jats:styled-content>\n                    ; therefore, further work is needed to fully understand effects on tenofovir pharmacodynamics.\n                  <\/jats:p>","DOI":"10.1111\/cts.70597","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:23:39Z","timestamp":1779107019000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>\n                      <i>Prevotella bivia<\/i>\n                    <\/scp>\n                    Influences Antiretroviral Pharmacokinetics and Viral Replication in an Ex\u00a0Vivo Vaginal Tissue Model"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-0009","authenticated-orcid":false,"given":"Alyssa M.","family":"Lantz","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy, University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5448-9207","authenticated-orcid":false,"given":"Lindsey B.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy, University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-0421","authenticated-orcid":false,"given":"Elizabeth B.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy, University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2309-0083","authenticated-orcid":false,"given":"Christopher","family":"Staley","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical School University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5513-5509","authenticated-orcid":false,"given":"Melanie R.","family":"Nicol","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy, University of Minnesota  Minneapolis Minnesota 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