{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T01:54:58Z","timestamp":1775699698249,"version":"3.50.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["2U01AI069924"],"award-info":[{"award-number":["2U01AI069924"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["174281"],"award-info":[{"award-number":["174281"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["BSSGI0_155851"],"award-info":[{"award-number":["BSSGI0_155851"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG\u2019s high genetic barrier to resistance. We used mathematical modeling to predict the impact of the scale-up of DTG-based ART on NNRTI pretreatment drug resistance (PDR) in South Africa, 2020 to 2040.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>We adapted the Modeling Antiretroviral drug Resistance In South Africa (MARISA) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modeled the introduction of DTG in 2020 under 2 scenarios: DTG as first-line regimen for ART initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Given the safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to (1) women beyond reproductive age; (2) women beyond reproductive age or using contraception; and (3) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI PDR in all scenarios if ART initiators are started on a DTG-based regimen, and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI PDR would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI PDR from 52.4% (without DTG) to 10.4% (with universal DTG) in 2040. If only men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI PDR would reach 25.9% in 2040. Limitations include substantial uncertainty due to the long-term predictions and the current scarcity of knowledge about DTG efficacy in South Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels, whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would only slow down the increase in levels of NNRTI PDR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1003397","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T13:24:40Z","timestamp":1607952280000},"page":"e1003397","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Impact of scaling up dolutegravir on antiretroviral resistance in South Africa: A modeling study"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7221-1929","authenticated-orcid":true,"given":"Anthony","family":"Hauser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4638-1940","authenticated-orcid":true,"given":"Katharina","family":"Kusejko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2717-011X","authenticated-orcid":true,"given":"Leigh F.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-6723","authenticated-orcid":true,"given":"Huldrych F.","family":"G\u00fcnthard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3808-2852","authenticated-orcid":true,"given":"Julien","family":"Riou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Wandeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-5132","authenticated-orcid":true,"given":"Matthias","family":"Egger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-8348","authenticated-orcid":true,"given":"Roger D.","family":"Kouyos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"issue":"8","key":"pmed.1003397.ref001","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1136\/sextrans-2014-051991","article-title":"Estimating the impact of the US President\u2019s Emergency Plan for AIDS Relief on HIV treatment and prevention programmes in Africa.","volume":"91","author":"LM Heaton","year":"2015","journal-title":"Sex Transm Infect"},{"issue":"12","key":"pmed.1003397.ref002","doi-asserted-by":"crossref","first-page":"e1002468","DOI":"10.1371\/journal.pmed.1002468","article-title":"Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study","volume":"14","author":"LF Johnson","year":"2017","journal-title":"PLoS Med"},{"key":"pmed.1003397.ref003","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.eclinm.2019.03.006","article-title":"Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000\u20132016: A Pooled Sequence Analysis","volume":"9","author":"B Chimukangara","year":"2019","journal-title":"EClinicalMedicine"},{"issue":"9","key":"pmed.1003397.ref004","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1093\/infdis\/jix089","article-title":"Impact of HIV Drug Resistance on HIV\/AIDS-Associated Mortality, New Infections, and Antiretroviral Therapy Program Costs in Sub-Saharan Africa","volume":"215","author":"AN Phillips","year":"2017","journal-title":"J Infect Dis"},{"key":"pmed.1003397.ref005","unstructured":"South Africa National Department of Health. 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