{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:07:08Z","timestamp":1790766428998,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>A vaginal ring containing 25\u00a0mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women\u2019s risk of sexually acquiring HIV\u20101; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured the amount of dapivirine in returned rings from a placebo\u2010controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I\/II studies established that greater than 4\u00a0mg of dapivirine on average is released from the ring when used consistently over 28\u00a0days and \u22640.9\u00a0mg released suggested non\u2010use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time\u2010dependent covariate for HIV\u20101 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV\u20101 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Residual dapivirine levels indicating at least some use (&gt;0.9\u00a0mg released over a month) were associated with a 48% relative reduction in HIV\u20101 acquisition risk (95% confidence interval (CI): 21% to 66%; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV\u20101 acquisition estimated 75% to 91% HIV\u20101 risk reduction with&gt;\u00a04\u00a0mg released when compared to placebo. Results limited to the subgroup of women &lt;25\u00a0years of age, who tended to have lower adherence, were generally consistent to those overall.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Residual dapivirine levels, an objective measure of adherence, were correlated with HIV\u20101 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long\u2010acting, woman\u2010initiated approach for discreet HIV\u20101 prevention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25634","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T20:58:55Z","timestamp":1605733135000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV\u20101 acquisition: a secondary analysis from a randomized, placebo\u2010controlled trial"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4286-2111","authenticated-orcid":false,"given":"Elizabeth R","family":"Brown","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease and Public Health Sciences Divisions Fred Hutchinson Cancer Research Center Seattle WA USA"},{"name":"Department of Biostatistics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5696-8665","authenticated-orcid":false,"given":"Craig W","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins University Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8536-648X","authenticated-orcid":false,"given":"Ariane","family":"van der Straten","sequence":"additional","affiliation":[{"name":"Women's Global Health Imperative RTI International San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-4353","authenticated-orcid":false,"given":"Flavia M","family":"Kiweewa","sequence":"additional","affiliation":[{"name":"Makerere University\u2010Johns Hopkins University Research Collaboration Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyaradzo M","family":"Mgodi","sequence":"additional","affiliation":[{"name":"University of Zimbabwe College of Health Sciences Clinical Trials Research Centre Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thesla","family":"Palanee\u2010Philips","sequence":"additional","affiliation":[{"name":"Wits Reproductive Health and HIV Research Institute School of Clinical Medicine University of the Witswatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Marzinke","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins University Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-4386","authenticated-orcid":false,"given":"Linda\u2010Gail","family":"Bekker","sequence":"additional","affiliation":[{"name":"Desmond Tutu HIV Foundation Clinical Research Site Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Soto\u2010Torres","sequence":"additional","affiliation":[{"name":"Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L","family":"Hillier","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine and Magee\u2010Womens Research Institute Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8242-8438","authenticated-orcid":false,"given":"Jared M","family":"Baeten","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Epidemiology, and Global Health University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the MTN\u2010020\/ASPIRE Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"UNAIDS.Women and Girls and HIV.Geneva Switzerland:Joint United Nations Programme on HIV\/AIDS;2018."},{"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\/NEJMoa1011205"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000219"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506110"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602046"},{"key":"e_1_2_9_8_1","unstructured":"BaetenJ Palanee\u2010PhillipsT MgodiN RamjeeB GatiF MhlangaP et al.High adherence and sustained impact on HIV\u20101 incidence: Final results of an open\u2010label extension trial of the dapivirine vaginal ring. IAS 2019: 10th IAS Conference on HIV Science. Mexico City Mexico;2019."},{"key":"e_1_2_9_9_1","unstructured":"NelA MalherbeM MansW et al.Safety adherence and HIV\u20101 seroconversion in DREAM\u2014an open\u2010label dapivirine vaginal ring trial. 9th South African AIDS Conference;2019s."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182986f69"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70847-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000172"},{"key":"e_1_2_9_13_1","unstructured":"WHO.Guideline on when to start antiretroviral therapy and on pre\u2010exposure prophylaxis for HIV.2015. [cited 2002 Oct 26]. Available from:http:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/186275\/9789241509565_eng.pdf;jsessionid=E57E17E2CF940BC43AA925A899C860FF?sequence=1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000280"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181acb536"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128857"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.256"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2016.03.023"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0081-1750.2004.00151.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002099"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000158"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2015.0182"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001503"},{"issue":"3","key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/infdis\/jiv333","article-title":"Pharmacological measures of treatment adherence and risk of HIV infection in the VOICE study","volume":"213","author":"Dai JY","year":"2015","journal-title":"J Infect Dis"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.9745\/GHSP-D-13-00010"}],"container-title":["Journal of the International AIDS Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jia2.25634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jia2.25634","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jia2.25634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:02:27Z","timestamp":1693803747000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jia2.25634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/jia2.25634"],"URL":"https:\/\/doi.org\/10.1002\/jia2.25634","archive":["Portico"],"relation":{},"ISSN":["1758-2652","1758-2652"],"issn-type":[{"value":"1758-2652","type":"print"},{"value":"1758-2652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"2020-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e25634"}}