{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:21:51Z","timestamp":1776291711589,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI120765"],"award-info":[{"award-number":["R01 AI120765"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AI027757"],"award-info":[{"award-number":["P30 AI027757"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24 AI136618"],"award-info":[{"award-number":["R24 AI136618"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007813","name":"University of Washington Center for AIDS Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007813","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Washington Royalty Research Fund","award":["A92723"],"award-info":[{"award-number":["A92723"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Integrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways are well-defined for HIV-1, mutations that emerge in HIV-2 in response to INIs are incompletely characterized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed systematic searches of GenBank and HIV-2 drug resistance literature to identify treatment-associated mutations for phenotypic evaluation. We then constructed a library of 95 mutants of HIV-2ROD9 that contained single or multiple amino acid changes in the integrase protein. Each variant was tested for susceptibility to raltegravir and dolutegravir using a single-cycle indicator cell assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed extensive cross-resistance between raltegravir and dolutegravir in HIV-2ROD9. HIV-2\u2013specific integrase mutations Q91R, E92A, A153G, and H157Q\/S, which have not been previously characterized, significantly increased the half maximum effective concentration (EC50) for raltegravir when introduced into 1 or more mutational backgrounds; mutations E92A\/Q, T97A, and G140A\/S conferred similar enhancements of dolutegravir resistance. HIV-2ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our analysis demonstrates the contributions of novel INI-associated mutations to raltegravir and dolutegravir resistance in HIV-2. These findings should help to improve algorithms for genotypic drug resistance testing in HIV-2\u2013infected individuals.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiac037","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T20:11:45Z","timestamp":1643400705000},"page":"497-509","source":"Crossref","is-referenced-by-count":7,"title":["Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants"],"prefix":"10.1093","volume":"226","author":[{"given":"Robert A","family":"Smith","sequence":"first","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent H","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana N","family":"Raugi","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khardiata","family":"Diallo Mbaye","sequence":"additional","affiliation":[{"name":"Service des Maladies Infectieuses et Tropicales, Centre Hospitalier National Universitaire de Fann , Dakar , Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moussa","family":"Seydi","sequence":"additional","affiliation":[{"name":"Service des Maladies Infectieuses et Tropicales, Centre Hospitalier National Universitaire de Fann , Dakar , Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey S","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Global Health, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"2022082618085518800_CIT0001","article-title":"2020 Global AIDS update\u2014seizing the moment\u2014tackling entrenched inequalities to end epidemics","author":"World Health"},{"key":"2022082618085518800_CIT0002","doi-asserted-by":"crossref","first-page":"e390","DOI":"10.1016\/S2352-3018(18)30094-8","article-title":"90-90-90 for HIV-2? Ending the HIV-2 epidemic by enhancing care and clinical management of patients infected with HIV-2.","volume":"5","author":"Gottlieb","year":"2018","journal-title":"Lancet HIV"},{"key":"2022082618085518800_CIT0003","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.meegid.2016.08.010","article-title":"HIV-2 molecular epidemiology.","volume":"46","author":"Visseaux","year":"2016","journal-title":"Infect Genet Evol"},{"key":"2022082618085518800_CIT0004","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/cid\/ciaa275","article-title":"Human immunodeficiency virus-2 (HIV-2): a summary of the present standard of care and treatment options for individuals living with HIV-2 in western Europe.","volume":"72","author":"Berzow","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2022082618085518800_CIT0005","article-title":"Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early 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