{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:45:14Z","timestamp":1777927514876,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["5TL1TR002318-02"],"award-info":[{"award-number":["5TL1TR002318-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P2C HD042828"],"award-info":[{"award-number":["P2C HD042828"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI068615"],"award-info":[{"award-number":["UM1AI068615"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI068633"],"award-info":[{"award-number":["UM1AI068633"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI106707"],"award-info":[{"award-number":["UM1AI106707"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J STD AIDS"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Women-initiated HIV \u2013 1 prevention products are key to reducing women\u2019s HIV-1 risk. Clinical trials of vaginal microbicides have shown limited to no efficacy in intention-to-treat (ITT) analyses. It is hypothesized that these negative results are partly due to efficacy dilution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a microsimulation model of MTN-020\/ASPIRE, a phase 3 trial that evaluated monthly use of a dapivirine vaginal ring for HIV-1 prevention. We evaluated four sources of efficacy dilution: trial-level factors: (i) an imbalance in the number of monthly sex acts between study arms and (ii) heterogeneity in risk emergent over time; and individual-level factors: (iii) product non-adherence and (iv) receptive anal intercourse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Assuming 70% per-vaginal exposure efficacy (consistent with the ITT estimate of 27%), heterogeneity in risk accounted for the largest proportion of efficacy dilution, at 42% (90% CrI: 38, 45), followed by non-adherence (33%; 90% CrI: 27, 39), an imbalance in arms (18%; 90% CrI: 16, 21) and lastly, anal intercourse with less than 10% of efficacy dilution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that heterogeneity in risk was the most important source of efficacy dilution in the ASPIRE trial. Future trials of HIV-1 prevention products for women should consider alternative trial designs and analytic approaches that minimize bias introduced by heterogeneity in risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09564624241300199","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T13:55:04Z","timestamp":1732629304000},"page":"195-204","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Understanding the sources of efficacy dilution in a trial of a monthly dapivirine vaginal ring for HIV-1 prevention"],"prefix":"10.1177","volume":"36","author":[{"given":"Kathryn","family":"Peebles","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4495-7245","authenticated-orcid":false,"given":"Laura","family":"Matrajt","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA"},{"name":"Department of Applied Mathematics, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared M","family":"Baeten","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"},{"name":"Department of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thesla","family":"Palanee-Phillips","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA"},{"name":"Wits RHI, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth R","family":"Brown","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA"},{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA"},{"name":"Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the MTN-020\/ASPIRE Study Team","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"bibr1-09564624241300199","volume-title":"Joint united nations programme on HIV\/AIDS 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