{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:08:35Z","timestamp":1780333715223,"version":"3.54.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Young men who have sex with men (YMSM) are disproportionately affected by human immunodeficiency virus (HIV); however, use of oral preexposure prophylaxis (PrEP) remains suboptimal. This study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of a novel tenofovir (TFV) rectal microbicide douche for HIV prevention.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Eight HIV-negative YMSM (aged 18\u201324 years) participated in a single-dose, open-label trial. Each received 660\u2005mg of TFV in a 125-mL rectal douche. Safety was assessed via clinical monitoring and adverse event (AE) reporting. PK analysis measured TFV and TFV-diphosphate (TFV-DP) concentrations in blood and rectal tissue. PD was evaluated using ex vivo HIV-1 challenge assays in rectal biopsies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>No serious AEs occurred. Five mild to moderate AEs (eg, nausea, hyperglycemia) were reported, none related to the product. Median peak plasma TFV concentration (14.5\u2005ng\/mL) remained below levels seen with oral TDF. Median peak (24-hour) rectal tissue cell TFV-DP concentrations were 8319\u2005fmol\/106 cells with a corresponding 0.9\u2005log10 HIV-1 p24 antigen reduction observed in ex vivo challenge assays. Rectal tissue TFV-DP concentrations exceeded those associated with on-demand oral 2-1-1 dosing from 1 to 72\u2005hours and suppressed HIV-1 p24 antigen production in colonic explants. Acceptability was high: 87.5% reported satisfaction, and 75% would consider future use.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The TFV rectal douche was safe, well tolerated, and acceptable to YMSM. Its favorable PK and PD profiles support further investigation as a behaviorally congruent, on-demand PrEP strategy. Additional studies are needed to assess long-term safety and efficacy in larger, more diverse populations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT04686279.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf349","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T20:02:09Z","timestamp":1751054529000},"page":"826-834","source":"Crossref","is-referenced-by-count":1,"title":["Safety, Pharmacokinetics, and Acceptability of a Tenofovir Rectal Microbicide Douche Among Young Men Who Have Sex With Men: The DREAM ATN Study (ATN 163)"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-2306","authenticated-orcid":false,"given":"Jose A","family":"Bauermeister","sequence":"first","affiliation":[{"name":"School of Nursing, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Arrington-Sanders","sequence":"additional","affiliation":[{"name":"School of Nursing, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]},{"name":"Craig-Dalsimer Division of Adolescent Medicine, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Coleman-Lewis","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn N","family":"Bertagnolli","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-1319","authenticated-orcid":false,"given":"Sandra","family":"Massih","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-8786","authenticated-orcid":false,"given":"Mark A","family":"Marzinke","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Fuchs","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-8128","authenticated-orcid":false,"given":"Ruohui","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy","family":"Anderson","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Addison","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeng H","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Breakey","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hoffman","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1478-1031","authenticated-orcid":false,"given":"Rahul P","family":"Bakshi","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M","family":"Zak","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Beselman","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6174-4060","authenticated-orcid":false,"given":"Willey","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Nursing, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison L","family":"Agwu","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University , Baltimore, Maryland 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Correlates of preferences for next-generation HIV prevention products among a national U.S. Sample of young men who have sex with men","volume":"26","author":"Biello","year":"2023","journal-title":"J Int AIDS Soc"},{"key":"2025101515135072100_jiaf349-B7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11904-020-00497-z","article-title":"PrEP product acceptability and dual process decision-making among men who have sex with men","volume":"17","author":"Bauermeister","year":"2020","journal-title":"Curr HIV\/AIDS Rep"},{"key":"2025101515135072100_jiaf349-B8","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1093\/infdis\/jiad535","article-title":"Tenofovir douche as HIV preexposure prophylaxis for receptive anal intercourse: safety, acceptability, pharmacokinetics, and pharmacodynamics (DREAM 01)","volume":"229","author":"Weld","year":"2024","journal-title":"J Infect 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