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We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide\/elvitegravir (TAF\/EVG, 20\u2005mg\/16\u2005mg) insert administered rectally.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MTN-039 was a phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid, and rectal tissue were collected over 72\u2005hours following rectal administration of 1 and 2 TAF\/EVG inserts for each participant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>TAF\/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4\u2005ng\/mL and TFV 4.4\u2005ng\/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9\u2005ng\/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high &amp;gt;2000\u2005fmol\/million cells for 72 hours with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each time point for both 1 and 2 inserts (P &amp;lt; .065 and P &amp;lt; .039, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Rectal administration of TAF\/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72\u2005hours.<\/jats:p>\n                  <jats:p>Clinical Trials Registration . NCT04047420.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiae211","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T10:32:25Z","timestamp":1713954745000},"page":"696-705","source":"Crossref","is-referenced-by-count":5,"title":["A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide\/Elvitegravir Insert Administered Rectally for HIV Prevention"],"prefix":"10.1093","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2545-7037","authenticated-orcid":false,"given":"Sharon A","family":"Riddler","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifton W","family":"Kelly","sequence":"additional","affiliation":[{"name":"Statistical Center for HIV\/AIDS Research and Prevention, Fred Hutchinson Cancer Center , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig J","family":"Hoesley","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, Alabama ,","place":["USA"]},{"name":"Department of Medical Education, University of Alabama at Birmingham , Birmingham, Alabama ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken S","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanna M","family":"Piper","sequence":"additional","affiliation":[{"name":"Division of AIDS, National Institute of Allergy and Infectious Diseases , Bethesda, Maryland 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,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1200-8494","authenticated-orcid":false,"given":"Peter L","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhonda M","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]},{"name":"Magee-Womens Research Institute , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratiya Pamela","family":"Kunjara Na Ayudhya","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A","family":"Bauermeister","sequence":"additional","affiliation":[{"name":"Department of Family and Community Health, University of Pennsylvania School of Nursing , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon L","family":"Hillier","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute , Pittsburgh, Pennsylvania ,","place":["USA"]},{"name":"Department of Obstetrics and Gynecology, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig W","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Medicine, Clinical Pharmacology, Johns Hopkins University , Baltimore, Maryland 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