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Rectal microbicides formulated as douches offer a behaviorally congruent alternative by leveraging existing douching practices. This study assessed the acceptability of a tenofovir-based rectal microbicide douche among YMSM. Eight YMSM (M\u2009=\u200920.9 years; range 18\u201324 years) participated in a Phase I, open-label, single-arm trial evaluating the safety, pharmacokinetics, and tolerability of a single 600\u00a0mg dose of tenofovir delivered in a 125mL rectal douche (NCT04686279). This mixed-methods study included post-dosing behavioral surveys and qualitative in-depth interviews (IDIs) to assess acceptability, tolerability, and perceptions of the product\u2019s usability. Interviews were transcribed, coded, and analyzed thematically. Descriptive statistics summarized participant characteristics, douching behaviors, and willingness to use the product in different contexts. Participants reported high acceptability of the rectal microbicide douche, particularly its ease of use and integration into existing sexual health routines. Most (87.5%) indicated they would find the product acceptable for HIV prevention, and 75% reported they would likely use it before every receptive anal intercourse (RAI) event. The episodic dosing regimen was perceived as a benefit, especially for casual sexual encounters. Barriers included product design concerns, privacy, and cost. A rectal microbicide douche was highly acceptable among YMSM, supporting its potential as a novel HIV prevention strategy. Findings underscore the importance of behaviorally congruent interventions and highlight key considerations for future product development, including improved packaging, affordability, and accessibility.<\/jats:p>\n          <jats:p>Trials Registration: NCT04686279.<\/jats:p>","DOI":"10.1007\/s10461-025-04763-2","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T01:47:42Z","timestamp":1748483262000},"page":"3114-3124","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessing the Acceptability of a Tenofovir-Based Rectal Microbicide Douche among Young Men who Have Sex with Men: Results from ATN-DREAM (ATN 163)"],"prefix":"10.1007","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-2306","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Bauermeister","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willey","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Webster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis L.","family":"Listerud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Burgese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Agwu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica Coleman","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuy","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Hightow-Weidman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Hendrix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Arrington-Sanders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"9","key":"4763_CR1","doi-asserted-by":"publisher","first-page":"2970","DOI":"10.1007\/s10461-024-04384-1","volume":"28","author":"J Hill-Rorie","year":"2024","unstructured":"Hill-Rorie J, Biello KB, Quint M, Johnson B, Elopre L, Johnson K, et al. Weighing the options: which PrEP (Pre-exposure Prophylaxis) modality attributes influence choice for young gay and bisexual men in the united States? AIDS Behav. 2024;28(9):2970\u20138.","journal-title":"AIDS Behav"},{"issue":"11","key":"4763_CR2","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1089\/apc.2022.0111","volume":"36","author":"PK Valente","year":"2022","unstructured":"Valente PK, Bauermeister JA, Lin WY, Silva DTD, Hightow-Weidman L, Drab R, et al. Preferences across Pre-Exposure prophylaxis modalities among young men who have sex with men in the united States: A latent class analysis study. AIDS Patient Care STDS. 2022;36(11):431\u201342.","journal-title":"AIDS Patient Care STDS"},{"issue":"10","key":"4763_CR3","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1007\/s10461-022-03665-x","volume":"26","author":"PK Valente","year":"2022","unstructured":"Valente PK, Bauermeister JA, Lin WY, Operario D, Rusley J, Hightow-Weidman L, et al. Next generation Pre-Exposure prophylaxis for young men who have sex with men: lessons from system and Provider-level barriers to oral PrEP. AIDS Behav. 2022;26(10):3422\u201335.","journal-title":"AIDS Behav"},{"issue":"6","key":"4763_CR4","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1007\/s10461-020-03106-7","volume":"25","author":"S Meanley","year":"2021","unstructured":"Meanley S, Connochie D, Choi SK, Bonett S, Flores DD, Bauermeister JA. Assessing the role of gay community attachment, stigma, and PrEP stereotypes on young men who have sex with men\u2019s PrEP uptake. AIDS Behav. 2021;25(6):1761\u201376.","journal-title":"AIDS Behav"},{"issue":"3","key":"4763_CR5","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1080\/08964289.2020.1731675","volume":"47","author":"S Meanley","year":"2021","unstructured":"Meanley S, Chandler C, Jaiswal J, Flores DD, Stevens R, Connochie D, et al. 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