{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:05:21Z","timestamp":1792292721901,"version":"4.4.0"},"reference-count":77,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["2R24AI13661806"],"award-info":[{"award-number":["2R24AI13661806"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) rarely leads to virological failure (VF) and drug resistance in integrase strand transfer inhibitor (INSTI)-na\u00efve persons living with HIV (PLWH). As a result, limited data are available on INSTI-associated drug resistance mutations (DRMs) selected by DTG-containing ART regimens. Methods: We reviewed studies published through July 2023 to identify those reporting emergent major INSTI-associated DRMs in INSTI-na\u00efve PLWH receiving DTG and those containing in vitro DTG susceptibility results using a standardized assay. Results: We identified 36 publications reporting 99 PLWH in whom major nonpolymorphic INSTI-associated DRMs developed on a DTG-containing regimen and 21 publications containing 269 in vitro DTG susceptibility results. DTG-selected DRMs clustered into four largely non-overlapping mutational pathways characterized by mutations at four signature positions: R263K, G118R, N155H, and Q148H\/R\/K. Eighty-two (82.8%) viruses contained just one signature DRM, including R263K (n = 40), G118R (n = 24), N155H (n = 9), and Q148H\/R\/K (n = 9). Nine (9.1%) contained \u22651 signature DRM, and eight (8.1%) contained just other DRMs. R263K and G118R were negatively associated with one another and with N155H and Q148H\/K\/R. R263K alone conferred a median 2.0-fold (IQR: 1.8\u20132.2) reduction in DTG susceptibility. G118R alone conferred a median 18.8-fold (IQR:14.2\u201323.4) reduction in DTG susceptibility. N155H alone conferred a median 1.4-fold (IQR: 1.2\u20131.6) reduction in DTG susceptibility. Q148H\/R\/K alone conferred a median 0.8-fold (IQR: 0.7\u20131.1) reduction in DTG susceptibility. Considerably higher levels of reduced susceptibility often occurred when signature DRMs occurred with additional INSTI-associated DRMs. Conclusions: Among INSTI-na\u00efve PLWH with VF and treatment emergent INSTI-associated DRMs, most developed one of four signature DRMs, most commonly R263K or G118R. G118R was associated with a much greater reduction in DTG susceptibility than R263K.<\/jats:p>","DOI":"10.3390\/v15091932","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:36:45Z","timestamp":1694932605000},"page":"1932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Treatment Emergent Dolutegravir Resistance Mutations in Individuals Na\u00efve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review"],"prefix":"10.3390","volume":"15","author":[{"given":"Kaiming","family":"Tao","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-6542","authenticated-orcid":false,"given":"Soo-Yon","family":"Rhee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, University of California San Francisco, San Francisco, CA 94011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava","family":"Avalos","sequence":"additional","affiliation":[{"name":"Careen Center for Health, Gaborone, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrit K.","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-2643","authenticated-orcid":false,"given":"Robert W.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/jama.2022.22246","article-title":"Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society\u2013USA Panel","volume":"329","author":"Gandhi","year":"2022","journal-title":"JAMA"},{"key":"ref_2","unstructured":"(2022, August 17). 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