{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:25:16Z","timestamp":1780525516192,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EDCTP2 Program","award":["RIA2016MC-1616-CHAPS"],"award-info":[{"award-number":["RIA2016MC-1616-CHAPS"]}]},{"name":"Gilead Sciences","award":["RIA2016MC-1616-CHAPS"],"award-info":[{"award-number":["RIA2016MC-1616-CHAPS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on protective efficacy in receptive sex, with limited research on the dosing requirements for insertive sex. We pre-clinically assessed the ex vivo pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) profile of tenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue. Methods: Inner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1BaL at a high (HVT) or a low viral titer (LVT). Infection was assessed by measurement of p24 in foreskin culture supernatants. TFV, TAF and TFV\u2013diphosphate (TFV\u2013DP) concentrations were measured in tissues, culture supernatants and dosing and washing solutions. Results: Dose\u2013response curves were obtained for both drugs, with greater potency observed against LVT. Inhibitory equivalency mimicking oral dosing was defined between 1 mg\/mL of TFV and 15 \u00b5g\/mL of TAF against HVT challenge. Concentrations of TFV\u2013DP in foreskin explants were approximately six-fold higher after ex vivo dosing with TAF than with TFV. Statistically significant negative linear correlations were observed between explant levels of TFV or TFV\u2013DP and p24 concentrations following HVT. Conclusions: Pre-clinical evaluation of TAF in foreskin explants revealed greater potency than TFV against penile HIV transmission. Clinical evaluation is underway to support this finding.<\/jats:p>","DOI":"10.3390\/pharmaceutics14061285","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T05:25:11Z","timestamp":1655443511000},"page":"1285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue"],"prefix":"10.3390","volume":"14","author":[{"given":"Laura","family":"Else","sequence":"first","affiliation":[{"name":"Bioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujan D.","family":"Penchala","sequence":"additional","affiliation":[{"name":"Bioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azure-Dee","family":"Pillay","sequence":"additional","affiliation":[{"name":"Division of Immunology, University of Cape Town, Cape Town 7935, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thabiso B.","family":"Seiphetlo","sequence":"additional","affiliation":[{"name":"Division of Immunology, University of Cape Town, Cape Town 7935, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6825-0573","authenticated-orcid":false,"given":"Limakatso","family":"Lebina","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suks","family":"Minhas","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust, Charing Cross Hospital, London W6 8RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Morley","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust, Charing Cross Hospital, London W6 8RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Rashid","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust, Charing Cross Hospital, London W6 8RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Martinson","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-8019","authenticated-orcid":false,"given":"Julie","family":"Fox","sequence":"additional","affiliation":[{"name":"Guys and St. Thomas\u2019 NHS Foundation Trust and King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-0967","authenticated-orcid":false,"given":"Saye","family":"Khoo","sequence":"additional","affiliation":[{"name":"Bioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3701-752X","authenticated-orcid":false,"given":"Carolina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Faculty of Medicine, Imperial College, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1056\/NEJMoa1506273","article-title":"On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection","volume":"373","author":"Molina","year":"2015","journal-title":"N. 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