{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:56:23Z","timestamp":1787500583022,"version":"build-2736575974"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir\/emtricitabine\/tenofovir alafenamide (BIC\/FTC\/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC\/FTC\/TAF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Clinical case report and review of the literature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A heavily treatment-experienced patient was switched to BIC\/FTC\/TAF due to drug\u2013drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1\u2005year after finishing treatment with raltegravir. Months after being switched to BIC\/FTC\/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20\u2005years, plasmatic viral load values are below 100\u2005copies\/mL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC\/FTC\/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae085","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T19:02:16Z","timestamp":1711998136000},"page":"1153-1156","source":"Crossref","is-referenced-by-count":12,"title":["Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir\/tenofovir alafenamide\/emtricitabine: case report and review of the literature"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-8014","authenticated-orcid":false,"given":"Luis","family":"Buzon-Martin","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Hospital Universitario de Burgos , Burgos 09006 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Navarro-San Francisco","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Hospital Universitario de Burgos , Burgos 09006 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Fernandez-Regueras","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Hospital Universitario de Burgos , Burgos 09006 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Sanchez-Gomez","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Hospital Universitario de Burgos , Burgos 09006 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"2024050202510110300_dkae085-B1","doi-asserted-by":"crossref","first-page":"e485","DOI":"10.1093\/cid\/ciaa988","article-title":"Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with human immunodeficiency virus","volume":"73","author":"Sax","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024050202510110300_dkae085-B2","doi-asserted-by":"crossref","first-page":"e389","DOI":"10.1016\/S2352-3018(20)30099-0","article-title":"Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomized, double-blind, multicenter, phase 3, non-inferiority trials","volume":"7","author":"Orkin","year":"2020","journal-title":"Lancet HIV"},{"key":"2024050202510110300_dkae085-B3","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/jac\/dkab481","article-title":"Real-life experience with bictegravir\/emtricitabine\/tenofovir alafenamide in a large reference clinical center","volume":"77","author":"Ambrosioni","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2024050202510110300_dkae085-B4","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/infdis\/jiab413","article-title":"Kinetics of archived M184V mutation in treatment-experienced virally suppressed HIV-infected patients","volume":"225","author":"Palich","year":"2022","journal-title":"J Infect Dis"},{"key":"2024050202510110300_dkae085-B5","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/jac\/dkac082","article-title":"Integrase resistance emergence with dolutegravir\/lamivudine with prior HIV-1 suppression","volume":"77","author":"Revollo","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2024050202510110300_dkae085-B6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1097\/QAD.0000000000003480","article-title":"Real-world use of dolutegravir two drug regimens","volume":"37","author":"Bowman","year":"2023","journal-title":"AIDS"},{"key":"2024050202510110300_dkae085-B7","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/hiv.13500","article-title":"Three-year efficacy of switching to dolutegravir plus lamivudine: a real-world study","volume":"24","author":"Palmier","year":"2023","journal-title":"HIV Med"},{"key":"2024050202510110300_dkae085-B8","first-page":"2239564","article-title":"Switching to dolutegravir\/lamivudine or bictegravir\/emtricitabine\/tenofovir alafenamide. A comparative real-world study","volume":"24","author":"Knobel","year":"2023","journal-title":"HIV Res Clin Pract"},{"key":"2024050202510110300_dkae085-B9","author":"Noe"},{"key":"2024050202510110300_dkae085-B10","doi-asserted-by":"crossref","first-page":"106039","DOI":"10.1016\/j.ijantimicag.2020.106039","article-title":"Previously unreported emergence of A265V substitution in the integrase gene in association with bictegravir virological failure","volume":"56","author":"Andr\u00e9-Garnier","year":"2020","journal-title":"Int J Antimicrob Agents"},{"key":"2024050202510110300_dkae085-B11","doi-asserted-by":"crossref","first-page":"104717","DOI":"10.1016\/j.antiviral.2020.104717","article-title":"Failure to bictegravir and development of resistance mutations in an antiretroviral-experienced patient","volume":"179","author":"Lozano","year":"2020","journal-title":"Antiviral Res"},{"key":"2024050202510110300_dkae085-B12","author":"Flanagan"},{"key":"2024050202510110300_dkae085-B13","author":"Rolle"},{"key":"2024050202510110300_dkae085-B14","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/S0140-6736(13)61221-0","article-title":"Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study","volume":"382","author":"Cahn","year":"2013","journal-title":"Lancet"},{"key":"2024050202510110300_dkae085-B15","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1128\/JVI.06591-11","article-title":"Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir","volume":"86","author":"Quashie","year":"2012","journal-title":"J Virol"},{"key":"2024050202510110300_dkae085-B16","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1742-4690-10-22","article-title":"Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure","volume":"10","author":"Mespl\u00e8de","year":"2013","journal-title":"Retrovirology"},{"key":"2024050202510110300_dkae085-B17","author":"Stanford University"},{"key":"2024050202510110300_dkae085-B18","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1093\/jac\/dkw109","article-title":"Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity","volume":"71","author":"Anstett","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2024050202510110300_dkae085-B19","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/jac\/dkx511","article-title":"Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen","volume":"73","author":"Charpentier","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2024050202510110300_dkae085-B20","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1093\/jac\/dkad319","article-title":"Virological outcomes of various first-line ART regimens in patients harboring HIV-1 E157Q integrase polymorphism: a multicenter retrospective study","volume":"78","author":"Uno","year":"2023","journal-title":"J Antimicrob Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/5\/1153\/57368021\/dkae085.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/5\/1153\/57368021\/dkae085.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T02:51:17Z","timestamp":1714618277000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/79\/5\/1153\/7638763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":20,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,4,1]]},"published-print":{"date-parts":[[2024,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae085","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2024,4,1]]}}}