{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T14:21:34Z","timestamp":1778422894583,"version":"3.51.4"},"reference-count":43,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Developing alternative approaches to evaluating absolute efficacy of new HIV prevention interventions is a priority, as active-controlled designs, whereby individuals without HIV are randomized to the experimental intervention or an active control known to be effective, are increasing. With this design, however, the efficacy of the experimental intervention to prevent HIV acquisition relative to placebo cannot be evaluated directly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One proposed approach to estimate absolute prevention efficacy is to use an HIV exposure marker, such as incident rectal gonorrhea, to infer counterfactual placebo HIV incidence. We formalize a statistical framework for this approach, specify working regression and likelihood-based estimation approaches, lay out three assumptions under which valid inference can be achieved, evaluate finite-sample performance, and illustrate the approach using a recent active-controlled HIV prevention trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We find that in finite samples and under correctly specified assumptions accurate and precise estimates of counterfactual placebo incidence and prevention efficacy are produced. Based on data from the DISCOVER trial in men and transgender women who have sex with men, and assuming correctly specified assumptions, the estimated prevention efficacy for tenofovir alafenamide plus emtricitabine is 98.1% (95% confidence interval: 96.4%\u201399.4%) using the working model approach and 98.1% (95% confidence interval: 96.4%\u201399.7%) using the likelihood-based approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Careful assessment of the underlying assumptions, study of their violation, evaluation of the approach in trials with placebo arms, and advancement of improved exposure markers are needed before the HIV exposure marker approach can be relied upon in practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745231203327","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T05:42:10Z","timestamp":1698212530000},"page":"114-123","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure"],"prefix":"10.1177","volume":"21","author":[{"given":"Yifan","family":"Zhu","sequence":"first","affiliation":[{"name":"Sanofi US, Bridgewater, NJ, USA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-5468","authenticated-orcid":false,"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David V","family":"Glidden","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Donnell","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Janes","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"bibr1-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17025"},{"key":"bibr2-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.2591"},{"key":"bibr3-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506110"},{"key":"bibr4-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602046"},{"key":"bibr5-17407745231203327","unstructured":"Hare CB, Coll J, Ruane P, et al. The phase 3 DISCOVER study: daily F\/TAF or F\/TDF for HIV preexposure prophylaxis, https:\/\/www.croiconference.org\/abstract\/phase-3-discover-study-daily-ftaf-or-ftdf-hiv-preexposure-prophylaxis\/"},{"key":"bibr6-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31065-5"},{"key":"bibr7-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101016"},{"key":"bibr8-17407745231203327","first-page":"8","volume":"24","author":"Delany-Moretlwe S","year":"2021","journal-title":"J Int AIDS Soc"},{"key":"bibr9-17407745231203327","unstructured":"The Joint United Nations Programme on HIV\/AIDS. Global HIV and AIDS statistics\u20142021 fact sheet, http:\/\/www.unaids.org\/en\/resources\/fact-sheet"},{"key":"bibr10-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu246"},{"key":"bibr11-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-016-2943-y"},{"key":"bibr12-17407745231203327","unstructured":"AIDS Vaccine Advocacy Coalition. The future of ARV-based prevention and more, https:\/\/www.avac.org\/infographic\/future-arv-basedprevention"},{"key":"bibr13-17407745231203327","unstructured":"World Health Organization. Ethical considerations in HIV prevention trials, https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/ethical-considerations-hiv-prevention-trials_en.pdf"},{"issue":"1","key":"bibr14-17407745231203327","first-page":"20190011","volume":"11","author":"Glidden DV","year":"2019","journal-title":"Stat Commun Infect Dis"},{"key":"bibr15-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30192-2"},{"key":"bibr16-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1315"},{"key":"bibr17-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2855"},{"key":"bibr18-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283509a29"},{"key":"bibr19-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1080\/15284336.2017.1379676"},{"key":"bibr20-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1177\/0962280218801134"},{"key":"bibr21-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031738"},{"key":"bibr22-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac7732"},{"key":"bibr23-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01953-6"},{"key":"bibr24-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz037"},{"issue":"1","key":"bibr25-17407745231203327","first-page":"12","volume":"11","author":"Murray J","year":"2019","journal-title":"Stat Commun Infect Dis"},{"key":"bibr26-17407745231203327","first-page":"4","volume":"11","author":"Janes H","year":"2019","journal-title":"Stat Commun Infect Dis"},{"key":"bibr27-17407745231203327","first-page":"7","volume":"11","author":"Follmann D","year":"2019","journal-title":"Stat Commun Infect Dis"},{"key":"bibr28-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz041"},{"key":"bibr29-17407745231203327","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000589"},{"key":"bibr30-17407745231203327","unstructured":"Public meeting webinar 3: protocol design considerations: analyses for ef\ufb01cacy: in-depth webinar report, https:\/\/forumresearch.org\/storage\/documents\/HIV_Forum\/Public_Meeting_Webinar_3_Report_Final_211027.pdf"},{"key":"bibr31-17407745231203327","unstructured":"U.S. Food and Drug Administration. 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