{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:29:58Z","timestamp":1787563798357,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"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\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["377790"],"award-info":[{"award-number":["377790"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"publisher","award":["BC-370929"],"award-info":[{"award-number":["BC-370929"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of Canada through Genome Canada and the Ontario Genomics Institute","award":["OGI-131"],"award-info":[{"award-number":["OGI-131"]}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Queen Elizabeth II Diamond Jubilee scholarship","award":["DLI O19375892122"],"award-info":[{"award-number":["DLI O19375892122"]}]},{"name":"International Ontario Graduate Scholarship international"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The second-generation integrase strand transfer inhibitor (INSTI) bictegravir is becoming accessible in low- and middle-income countries (LMICs), and another INSTI, cabotegravir, has recently been approved as a long-acting injectable. Data on bictegravir and cabotegravir susceptibility in raltegravir-experienced HIV-1 subtype A- and D-infected patients carrying drug resistance mutations (DRMs) remain very scarce in LMICs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>HIV-1 integrase (IN)-recombinant viruses from eight patients failing raltegravir-based third-line therapy in Uganda were genotypically and phenotypically tested for susceptibility to bictegravir and cabotegravir. Ability of these viruses to integrate into human genomes was assessed in MT-4 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HIV-1 IN-recombinant viruses harbouring single primary mutations (N155H or Y143R\/S) or in combination with secondary INSTI mutations (T97A, M50I, L74IM, E157Q, G163R or V151I) were susceptible to both bictegravir and cabotegravir. However, combinations of primary INSTI-resistance mutations such as E138A\/G140A\/G163R\/Q148R or E138K\/G140A\/S147G\/Q148K led to decreased susceptibility to both cabotegravir (fold change in EC50 values from 429 to 1000\u00d7) and bictegravir (60 to 100\u00d7), exhibiting a high degree of cross-resistance. However, these same IN-recombinant viruses showed impaired integration capacity (14% to 48%) relative to the WT HIV-1 NL4-3 strain in the absence of drug.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Though not currently widely accessible in most LMICs, bictegravir and cabotegravir offer a valid alternative to HIV-infected individuals harbouring subtype A and D HIV-1 variants with reduced susceptibility to first-generation INSTIs but previous exposure to raltegravir may reduce efficacy, more so with cabotegravir.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkab276","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T09:41:11Z","timestamp":1630143671000},"page":"2965-2974","source":"Crossref","is-referenced-by-count":18,"title":["High-level resistance to bictegravir and cabotegravir in subtype A- and D-infected HIV-1 patients failing raltegravir with multiple resistance mutations"],"prefix":"10.1093","volume":"76","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 University, London, Canada"},{"name":"Joint Clinical Research Centre, Kampala, Uganda"},{"name":"Center for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Avino","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abayomi S","family":"Olabode","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cissy M","family":"Kityo","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Kyeyune","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Kampala, Uganda"},{"name":"Center for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immaculate","family":"Nankya","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Kampala, Uganda"},{"name":"Center for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel E","family":"Qui\u00f1ones-Mateu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University, London, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4880-7968","authenticated-orcid":false,"given":"Eric J","family":"Arts","sequence":"additional","affiliation":[{"name":"Department of 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