{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:54:57Z","timestamp":1791849297214,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Bictegravir\/tenofovir alafenamide\/emtricitabine (BIC\/TAF\/FTC) is a complete regimen for the treatment of HIV with a high barrier to resistance and few reported cases of treatment failure. We present three cases of treatment\u2010emergent resistance to nucleoside\/nucleotide reverse transcriptase inhibitors (NRTIs) in patients with suboptimal treatment adherence and assess whether the resistance\u2010associated mutations were present before BIC\/TAF\/FTC initiation or emerged during therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used genotypic drug resistance testing by Sanger sequencing to identify emergent resistance mutations in plasma viral load specimens collected after combination antiretroviral therapy initiation in all participants. Additionally, we performed ultra\u2010deep sequencing by Illumina MiSeq on the earliest available plasma HIV\u20101 viral load specimen and on any available specimens closest in time to the initiation of BIC\/TAF\/FTC therapy to identify low\u2010abundance resistance mutations present in the viral quasispecies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All three participants developed NRTI resistance after prolonged exposure and incomplete adherence to BIC\/TAF\/FTC. The T69N, K70E, M184I, and\/or T215I mutations identified in clinical samples at the time of virological failure were not present on deep sequencing of either baseline samples or samples collected before BIC\/TAF\/FTC initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite a generally high genetic barrier to resistance, NRTI resistance\u2010associated mutations may emerge during therapy with BIC\/TAF\/FTC in the setting of suboptimal adherence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.13520","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T05:03:55Z","timestamp":1686805435000},"page":"1137-1143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Treatment\u2010emergent reverse transcriptase resistance during antiretroviral therapy with bictegravir, tenofovir alafenamide, and emtricitabine: A case series"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5522-4077","authenticated-orcid":false,"given":"Samuel","family":"DeKoven","sequence":"first","affiliation":[{"name":"Department of Family and Community Medicine St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Naccarato","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Henry Ford Hospital  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanson J.","family":"Brumme","sequence":"additional","affiliation":[{"name":"BC Centre for Excellence in HIV\/AIDS  Vancouver British Columbia Canada"},{"name":"Division of Infectious Diseases University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3069-2875","authenticated-orcid":false,"given":"Darrell H. S.","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, St. Michael's Hospital  Toronto Ontario Canada"},{"name":"MAP Centre for Urban Health Solutions, St. Michael's Hospital  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV","author":"Panel on Antiretroviral Guidelines for Adults and Adolescents","year":"2023"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01474-16"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-018-0440-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30077-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(18)30092-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz347"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002731"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz555"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13040583"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106039"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab297"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104717"},{"key":"e_1_2_9_14_1","unstructured":"StollM BraunP WiesmannF KnechtenH.Development of integrase inhibitor resistance under first\u2010line treatment with bictegravir. Poster presentation P125. HIV Glasgow 2020 Virtual. 5\u20138 October 20202020."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu019"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz060"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58544-z"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000180095.12276.ac"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","unstructured":"MulatoA AcostaRK YantSR CihlarT WhiteKL.Forgiveness of BIC\/FTC\/TAF: in vitro simulations of intermittent poor adherence find limited HIV\u20101 breakthrough and high barrier to resistance. Open forum infectious diseases. Conference: infectious diseases week IDWeek 2020.2020.","DOI":"10.1093\/ofid\/ofaa439.1629"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000003311"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa988"}],"container-title":["HIV Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hiv.13520","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T07:41:56Z","timestamp":1705909316000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hiv.13520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,14]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/hiv.13520"],"URL":"https:\/\/doi.org\/10.1111\/hiv.13520","archive":["Portico"],"relation":{},"ISSN":["1464-2662","1468-1293"],"issn-type":[{"value":"1464-2662","type":"print"},{"value":"1468-1293","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,14]]},"assertion":[{"value":"2023-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}