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We evaluated the potential epidemiological impact and cost\u2010effectiveness of dapivirine vaginal ring Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> among 22\u2010 to 45\u2010year\u2010old women in KwaZulu\u2010Natal, South Africa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using mathematical modelling, we studied dapivirine vaginal ring Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> implementation, either unprioritized, or prioritized based on <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> incidence (\u22653% per year), age (22 to 29\u00a0years) or female sex worker status, alongside the implementation of voluntary medical male circumcision and antiretroviral therapy scaled\u2010up to <jats:styled-content style=\"fixed-case\">UNAIDS<\/jats:styled-content> Fast\u2010Track targets. Outcomes over the intervention (2019 to 2030) and lifetime horizons included cumulative <jats:styled-content style=\"fixed-case\">HIV infect<\/jats:styled-content>ions, life\u2010years lived, costs and cost\u2010effectiveness. We assessed the incremental cost\u2010effectiveness ratios against the revealed willingness to pay ($500) and the standard (2017 per capita gross domestic product; $6161) cost\u2010effectiveness thresholds for South Africa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to a reference scenario without Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>, implementation of dapivirine vaginal ring Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>, assuming 56% effectiveness and covering 50% of 22 to 29\u2010year\u2010old or high\u2010incidence women, prevented 10% or 11% of infections by 2030 respectively. Equivalent, unprioritized coverage (30%) prevented fewer infections (7%), whereas 50% coverage of female sex workers had the least impact (4%). Drug resistance attributable to Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> was modest (2% to 4% of people living with drug\u2010resistant <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>). Over the lifetime horizon, dapivirine Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> implementation among female sex workers was cost\u2010saving, whereas incidence\u2010based Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> cost $1898 per life\u2010year gained, relative to Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> among female sex workers and $989 versus the reference scenario. In a scenario of 37% Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> effectiveness, Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> had less impact, but prioritization to female sex workers remained cost\u2010saving. In uncertainty analysis, female sex worker Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> was consistently cost\u2010saving; and over the lifetime horizon, Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> cost less than $6161 per life\u2010year gained in over 99% of simulations, whereas incidence\u2010 and age\u2010based Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> cost below $500 per life\u2010year gained in 61% and 49% of simulations respectively. Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> adherence and efficacy, and the effectiveness of antiretroviral therapy for <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> prevention, were the principal drivers of uncertainty in the cost\u2010effectiveness of Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dapivirine vaginal ring Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> would be cost\u2010saving in KwaZulu\u2010Natal if prioritized to female sex workers. Pr<jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content>'s impact on <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> prevention would be increased, with potential affordability, if prioritized to women by age or incidence.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25282","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T13:24:52Z","timestamp":1557494692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Dapivirine vaginal ring for <scp>HIV<\/scp> prevention: modelling health outcomes, drug resistance and cost\u2010effectiveness"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4936-0264","authenticated-orcid":false,"given":"Robert","family":"Glaubius","sequence":"first","affiliation":[{"name":"Departments of Quantitative Health Sciences and Infectious Disease Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Medicine Section\u00a0of Infectious Diseases and Department of Molecular Virology and Microbiology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri J","family":"Penrose","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases School of Medicine University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Hood","sequence":"additional","affiliation":[{"name":"Pittsburgh Supercomputing Center Carnegie Mellon University Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Engquist","sequence":"additional","affiliation":[{"name":"Center for Research Computing Rice University Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Mellors","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases School of Medicine University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-0629","authenticated-orcid":false,"given":"Urvi M","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases School of Medicine University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-3179","authenticated-orcid":false,"given":"Ume L","family":"Abbas","sequence":"additional","affiliation":[{"name":"Departments of Quantitative Health Sciences and Infectious Disease Cleveland Clinic Cleveland OH USA"},{"name":"Department of Medicine Section\u00a0of Infectious Diseases and Department of Molecular Virology and Microbiology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001145"},{"key":"e_1_2_9_3_1","volume-title":"Guideline on When to Start Antiretroviral Therapy and on Pre\u2010Exposure Prophylaxis for HIV","author":"World Health Organization","year":"2015"},{"key":"e_1_2_9_4_1","unstructured":"Medicines Control Council.Press release: Medicines Control Council approves fixed\u2010dose combination of tenofovir disoproxyl fumarate and emtricitabine for pre\u2010exposure prophylaxis of HIV.2015[cited 2017 Jul 3]. 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