{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:40:08Z","timestamp":1789501208922,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Randomized trials of new agents for HIV pre\u2010exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F\/TDF), without a placebo group. We used the well\u2010characterized adherence\u2010efficacy relationship for F\/TDF to back\u2010calculate the (non\u2010PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non\u2010inferiority of emtricitabine and tenofovir alafenamide (F\/TAF) to F\/TDF (HIV incidence rate ratio [IRR] 0\u00b747, 95% CI: 0\u00b719 to 1.15). Tenofovir diphosphate (TFV\u2010DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F\/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were six versus 11 postbaseline HIV infections (0.14 vs. 0.25\/100 person\u2010years [PY]) on F\/TAF and F\/TDF respectively. Of the 11 on F\/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV\u2010negative controls, 5% of the person\u2010time years had low, 9% had medium and 86% had high TFV\u2010DP levels. A non\u2010informative prior distribution for counterfactual bHIV, combined with the prior for TFV\u2010DP level\u2010efficacy relationship, yielded a posterior counterfactual bHIV of 3\u00b74 infections\/100 PY (0.80 Bayesian credible interval [CrI] 1\u00b79 to 5\u00b79), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F\/TAF and 93% (0.95 CrI [87% to 96%]) for F\/TDF compared to bHIV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non\u2010PrEP control group in randomized, active\u2010controlled PrEP trials that include a F\/TDF\u2010comparator group.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25744","type":"journal-article","created":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T04:59:21Z","timestamp":1621659561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Using the adherence\u2010efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background HIV incidence: a secondary analysis of a randomized, controlled trial"],"prefix":"10.1002","volume":"24","author":[{"given":"David V","family":"Glidden","sequence":"first","affiliation":[{"name":"School of Medicine University of California San Francisco San Francisco CA USA"},{"name":"Department of Epidemiology and Biostatistics San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moupali","family":"Das","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1836-4446","authenticated-orcid":false,"given":"David T","family":"Dunn","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research in Infection and Sexual Health Institute for Global Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Ebrahimi","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver T","family":"Stirrup","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research in Infection and Sexual Health Institute for Global Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared M","family":"Baeten","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Colorado Denver \u2010 Anschutz Medical Campus Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108524"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506273"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00056-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001129"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ778"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy210.1131"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001534"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001825"},{"key":"e_1_2_9_11_1","first-page":"49","article-title":"Should we fear resistance from tenofovir\/emtricitabine preexposure prophylaxis?","volume":"11","author":"Parikh UM","year":"2015","journal-title":"AIDS"},{"key":"e_1_2_9_12_1","unstructured":"Centers for Disease Control and Prevention.Effectiveness of prevention strategies to reduce the risk of acquiring or transmitting HIV[cited 2019 Nov 3]. Available from:https:\/\/www.cdc.gov\/hiv\/risk\/estimates\/preventionstrategies.html"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(18)30215-7"},{"key":"e_1_2_9_14_1","unstructured":"HighleymanL.PrEP scales Up HIV incidence declines.2018[cited 2019 Nov 3]. Available from:https:\/\/betablog.org\/prep\u2010scales\u2010up\u2010hiv\u2010incidence\u2010declines\/"},{"key":"e_1_2_9_15_1","unstructured":"New York City Department of Health and Mental Hygiene.HIV epidemiology annual report 2017.2018[cited 2019 Nov 3]. Available athttps:\/\/www.sfdph.org\/dph\/comupg\/oprograms\/HIVepiSec\/HIVepiSecReports.asp"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(17)30044-9"},{"key":"e_1_2_9_17_1","unstructured":"San Francisco Department of Public Health Population Health Division.HIV Epidemiology Annual Report 2017.2018[cited 2019 May 12]. Available from:https:\/\/www.sfdph.org\/dph\/files\/reports\/RptsHIVAIDS\/AnnualReport2017\u2010Green\u201020180904\u2010Web.pdf"},{"key":"e_1_2_9_18_1","unstructured":"SullivanPS SmithDK Mera\u2010GilerR et\u00a0al.The impact of pre\u2010exposure prophylaxis with TDF\/FTC on HIV diagnoses 2012\u20102016 United States [Abstract LBPEC036]. International AIDS Conference (IAC); 2018a 23\u201027 July; Amsterdam the Netherlands.2018[cited 2019 Nov 3]. Available from:http:\/\/www.natap.org\/2018\/IAC\/IAC_17.htm"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/09540121.2017.1300633"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001497"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31065-5"},{"key":"e_1_2_9_22_1","unstructured":"LandovitzRJ DonnellD ClementM HanscomL CottleL CoelhoR et\u00a0al.HPTN 083 Interim Results: Pre\u2010Exposure Prophylaxis (PrEP) Containing Long\u2010Acting Injectable Cabotegravir (CAB\u2010LA) Is Safe and Highly Effective for Cisgender Men and Transgender Women Who Have Sex with Men (MSM TGW). Presented at AIDS 2020 (Virtual) July 6\u201010. #OAXLB01. Available from:https:\/\/www.hptn.org\/presentedresearch\/AIDS2020"},{"key":"e_1_2_9_23_1","unstructured":"MurrayM AntelaA MillsA ChountaV HuangJ JaegerH et\u00a0al.Patient views on long acting HIV treatment: Cabotegravir + rilpivirine as maintenance therapy (ATLAS 48 week results). Presented at IAS 2019 (Mexico City MX) July 21\u201024. Available from:http:\/\/programme.ias2019.org\/Abstract\/Abstract\/3680"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31288-7"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz037"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002099"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30192-2"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70847-3"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/73.1.1"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2012.0089"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002354"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01710-17"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177012092"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/5.2.193"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v076.i01"},{"key":"e_1_2_9_36_1","volume-title":"A language and environment for statistical computing. R Foundation for Statistical Computing","author":"R Core Team. R","year":"2019"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000351"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(18)30045-6"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1515\/em-2015-0007"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix313"},{"key":"e_1_2_9_41_1","first-page":"20190011","article-title":"Advancing novel PrEP products \u2013 alternatives to non\u2010inferiority","volume":"11","author":"Glidden DV","year":"2019","journal-title":"Stat Commun Infect Dis"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000172"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25433"},{"key":"e_1_2_9_44_1","unstructured":"GaoF GliddenDV HughesJP DonnellD.Sample size calculation for active\u2010arm trial with counterfactual incidence based on recency Assay. Statistics > Methodology [cited 2020 Nov 20]. Available from:https:\/\/arxiv.org\/abs\/2011.00725"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280218801134"}],"container-title":["Journal of the International AIDS Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jia2.25744","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jia2.25744","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jia2.25744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T22:48:13Z","timestamp":1692830893000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jia2.25744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/jia2.25744"],"URL":"https:\/\/doi.org\/10.1002\/jia2.25744","archive":["Portico"],"relation":{},"ISSN":["1758-2652","1758-2652"],"issn-type":[{"value":"1758-2652","type":"print"},{"value":"1758-2652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"2020-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e25744"}}