{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:03:14Z","timestamp":1788433394644,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T00:00:00Z","timestamp":1539561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"publisher","award":["612216"],"award-info":[{"award-number":["612216"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"publisher","award":["MRC-RFA-UFSP-01-2013\/UKZN HIVEPI"],"award-info":[{"award-number":["MRC-RFA-UFSP-01-2013\/UKZN HIVEPI"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck & Co. Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; &lt;50 copies\/mL) in individuals prescribed primarily tenofovir\/emtricitabine\/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Among 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) &gt;1000 copies\/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PDR prevalence was 9.5% (109\/1148) and 12.8% (147\/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91\u20132.13), mostly on fixed-dose combination tenofovir\/emtricitabine\/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)\/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12\u20130.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82\u20131.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir\/emtricitabine\/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Tegistration<\/jats:title>\n                    <jats:p>NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciy881","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T07:50:14Z","timestamp":1539071414000},"page":"207-214","source":"Crossref","is-referenced-by-count":58,"title":["Impact of Next-generation Sequencing Defined Human Immunodeficiency Virus Pretreatment Drug Resistance on Virological Outcomes in the ANRS 12249 Treatment-as-Prevention Trial"],"prefix":"10.1093","volume":"69","author":[{"given":"Anne","family":"Derache","sequence":"first","affiliation":[{"name":"Africa Health Research Institute, Mtubatuba, South Africa"},{"name":"Sorbonne University, l\u2019universit\u00e9 Pierre et Marie Curie, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique Unit\u00e9 Mixte de Recherche en Sant\u00e9 (IPLESP UMRS 1136), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2045-1717","authenticated-orcid":false,"given":"Collins C","family":"Iwuji","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute, Mtubatuba, South Africa"},{"name":"Department of Global Health and Infection, Brighton and Sussex Medical School"},{"name":"Institute for Global Health, University College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Baisley","sequence":"additional","affiliation":[{"name":"Sorbonne University, l\u2019universit\u00e9 Pierre et Marie Curie, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique Unit\u00e9 Mixte de Recherche en Sant\u00e9 (IPLESP UMRS 1136), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siva","family":"Danaviah","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute, Mtubatuba, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Genevi\u00e8ve","family":"Marcelin","sequence":"additional","affiliation":[{"name":"Sorbonne University, l\u2019universit\u00e9 Pierre et Marie Curie, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique Unit\u00e9 Mixte de Recherche en Sant\u00e9 (IPLESP UMRS 1136), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Calvez","sequence":"additional","affiliation":[{"name":"Sorbonne University, l\u2019universit\u00e9 Pierre et Marie Curie, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique Unit\u00e9 Mixte de Recherche en Sant\u00e9 (IPLESP UMRS 1136), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3027-5254","authenticated-orcid":false,"given":"Tulio","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Innovation and Sequencing Platform, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Dabis","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Institut de Sant\u00e9 Publique d\u2019Epid\u00e9miologie et de D\u00e9veloppement, Centre Institut national de la sant\u00e9 et de la recherche m\u00e9dicale 1219, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kholoud","family":"Porter","sequence":"additional","affiliation":[{"name":"Institute for Global Health, University College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deenan","family":"Pillay","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute, Mtubatuba, South Africa"},{"name":"Division of Infection and Immunity, University College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"2019070201024969100_CIT0001","volume-title":"Global AIDS Update 2016","author":"World Health Organization"},{"key":"2019070201024969100_CIT0002","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1097\/QAI.0b013e31829ceb14","article-title":"Reduction in early mortality on antiretroviral therapy for adults in rural South Africa since change in 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Virologic suppression and emerging resistance on first-line antiretroviral therapy following universal test and treat: the ANRS 12249 cluster randomised trial. 9th IAS Conference on HIV Science. Paris, France, 2017."},{"key":"2019070201024969100_CIT0030","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":"Phillips","year":"2017","journal-title":"J Infect Dis"},{"key":"2019070201024969100_CIT0031","volume-title":"Guidelines on the public health response to pretreatment HIV drug resistance","author":"World Health Organization","year":"2016"},{"key":"2019070201024969100_CIT0032","volume-title":"New high-quality antiretroviral therapy to be launched in South Africa, Kenya and over 90 low-and middle-income countries at reduced price","author":"UNAIDS","year":"2017"},{"key":"2019070201024969100_CIT0033","doi-asserted-by":"crossref","first-page":"28","DOI":"10.7196\/SAMJ.2017.v107i1.12058","article-title":"Cutting the cost of South African antiretroviral therapy using newer, safer drugs","volume":"107","author":"Venter","year":"2016","journal-title":"S Afr Med J"},{"key":"2019070201024969100_CIT0034","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1097\/QAI.0000000000000790","article-title":"Dolutegravir plus abacavir\/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the SINGLE randomized clinical trial","volume":"70","author":"Walmsley","year":"2015","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2019070201024969100_CIT0035","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1056\/NEJMoa1215541","article-title":"Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection","volume":"369","author":"Walmsley","year":"2013","journal-title":"N Engl J Med"},{"key":"2019070201024969100_CIT0036","article-title":"Cevik M, McGann H. Dolutegravir use in combination with rifampicin-based tuberculosis therapy: 3 years of real-world experience in a large UK teaching hospital. 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