{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:49:46Z","timestamp":1792752586099,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T00:00:00Z","timestamp":1608854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1\u2010AI068641"],"award-info":[{"award-number":["UM1\u2010AI068641"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1\u2010AI120197"],"award-info":[{"award-number":["UM1\u2010AI120197"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1U01\u2010AI36780"],"award-info":[{"award-number":["1U01\u2010AI36780"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this analysis was to characterize transmitted drug resistance (TDR) in Strategic Timing of Antiretroviral Treatment (START) study participants by next\u2010generation sequencing (NGS), a sensitive assay capable of detecting low\u2010frequency variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Stored plasma from participants with entry HIV RNA\u00a0&gt;\u00a01000 copies\/mL were analysed by NGS (Illumina MiSeq). TDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase strand transfer inhibitor (INSTI) surveillance mutations (Stanford HIVdb). Drug resistance mutations (DRMs) detected at three thresholds are reported: &gt; 2%, 5% and 20% of the viral population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 2009 and 2013, START enrolled 4684 antiretroviral therapy (ART)\u2010na\u00efve individuals in 35 countries. Baseline NGS data at study entry were available for 2902 participants. Overall prevalence rates of TDR using a detection threshold of 2%\/5%\/20% were 9.2%\/5.6%\/3.2% for nucleoside reverse transcriptase inhibitors (NRTIs), 9.2%\/6.6%\/4.9% for non\u2010NRTIs, 11.4%\/5.5%\/2.4% for protease inhibitors (PIs) and 3.5%\/1.6%\/0.1% for INSTI DRMs and varied by geographic region. Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%). INSTI DRMs were detected almost exclusively below the 20% detection threshold, most commonly Y143H (0.4%), Q148R (0.4%) and T66I (0.4%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Use of NGS in this study population resulted in the detection of a large proportion of low\u2010level variants which would not have been detected by traditional Sanger sequencing. Global surveillance studies utilizing NGS should provide a more comprehensive assessment of TDR prevalence in different regions of the world.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.13038","type":"journal-article","created":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T07:53:45Z","timestamp":1608969225000},"page":"360-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transmitted HIV\u20101 drug resistance in a large international cohort using next\u2010generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0704-9603","authenticated-orcid":false,"given":"JD","family":"Baxter","sequence":"first","affiliation":[{"name":"Cooper University Hospital\/Cooper Medical School of Rowan University Camden NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Dunn","sequence":"additional","affiliation":[{"name":"Institute for Global Health UCL London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Tostevin","sequence":"additional","affiliation":[{"name":"Institute for Global Health UCL London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RL","family":"Marvig","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine Copenhagen University Hospital Rigshospitalet Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bennedb\u00e6k","sequence":"additional","affiliation":[{"name":"Copenhagen HIV Programme Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-919X","authenticated-orcid":false,"given":"A","family":"Cozzi\u2010Lepri","sequence":"additional","affiliation":[{"name":"Institute for Global Health UCL London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Biostatistics School of Public Health University of Minnesota Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MJ","family":"Kozal","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8006-325X","authenticated-orcid":false,"given":"M","family":"Gompels","sequence":"additional","affiliation":[{"name":"North Bristol NHS Trust Westbury on Trym UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-9490","authenticated-orcid":false,"given":"AN","family":"Pinto","sequence":"additional","affiliation":[{"name":"The Kirby Institute University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Lundgren","sequence":"additional","affiliation":[{"name":"Copenhagen HIV Programme Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the INSIGHT START Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000196172.35056.b7"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013552"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy463"},{"key":"e_1_2_6_5_1","first-page":"17","article-title":"Temporal changes in the epidemiology of transmission of drug\u2010resistant HIV\u20101 across the world","volume":"14","author":"Frentz D","year":"2012","journal-title":"AIDS Rev"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e328013caff"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283388742"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1310\/hct0801-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/427212"},{"key":"e_1_2_6_10_1","unstructured":"Organization WH.HIV Drug Resistance Report 2019. 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