{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T07:37:33Z","timestamp":1765438653428,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI-49170"],"award-info":[{"award-number":["AI-49170"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007813","name":"Center for AIDS Research","doi-asserted-by":"publisher","award":["P30 AI036219"],"award-info":[{"award-number":["P30 AI036219"]}],"id":[{"id":"10.13039\/100007813","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Webster Family Chair in Viral Pathogenesis"},{"name":"Government of Canada through Genome Canada"},{"DOI":"10.13039\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","award":["OGI-131"],"award-info":[{"award-number":["OGI-131"]}],"id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004381","name":"Western University","doi-asserted-by":"publisher","award":["DLI O19375892122"],"award-info":[{"award-number":["DLI O19375892122"]}],"id":[{"id":"10.13039\/501100004381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Increasing first-line treatment failures in low- and middle-income countries (LMICs) have led to increased use of integrase strand transfer inhibitors (INSTIs) such as dolutegravir. However, HIV-1 susceptibility to INSTIs in LMICs, especially with previous raltegravir exposure, is poorly understood due to infrequent reporting of INSTI failures and testing for INSTI drug resistance mutations (DRMs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 51 non-subtype B HIV-1 infected patients failing third-line (raltegravir-based) therapy in Uganda were initially selected for the study. DRMs were detected using Sanger and deep sequencing. HIV integrase genes of 13 patients were cloned and replication capacities (RCs) and phenotypic susceptibilities to dolutegravir, raltegravir and elvitegravir were determined with TZM-bl cells. Spearman\u2019s correlation coefficient was used to determine cross-resistance between INSTIs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>INSTI DRMs were detected in 47% of patients. HIV integrase-recombinant virus carrying one primary INSTI DRM (N155H or Y143R\/S) was susceptible to dolutegravir but highly resistant to raltegravir and elvitegravir (&amp;gt;50-fold change). Two patients, one with E138A\/G140A\/Q148R\/G163R and one with E138K\/G140A\/S147G\/Q148K, displayed the highest reported resistance to raltegravir, elvitegravir and even dolutegravir. The former multi-DRM virus had WT RC whereas the latter had lower RCs than WT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In HIV-1 subtype A- and D-infected patients failing raltegravir and harbouring INSTI DRMs, there is high-level resistance to elvitegravir and raltegravir. More routine monitoring of INSTI treatment may be advised in LMICs, considering that multiple INSTI DRMs may have accumulated during prolonged exposure to raltegravir during virological failure, leading to high-level INSTI resistance, including dolutegravir resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa355","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T19:14:39Z","timestamp":1595531679000},"page":"3525-3533","source":"Crossref","is-referenced-by-count":19,"title":["Accumulation of integrase strand transfer inhibitor resistance mutations confers high-level resistance to dolutegravir in non-B subtype HIV-1 strains from patients failing raltegravir in Uganda"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-9402","authenticated-orcid":false,"given":"Emmanuel","family":"Ndashimye","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Western 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Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Meadows","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul S","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cissy M","family":"Kityo","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Kyeyune","sequence":"additional","affiliation":[{"name":"Center for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immaculate","family":"Nankya","sequence":"additional","affiliation":[{"name":"Center for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel E","family":"Qui\u00f1ones-Mateu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, 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