{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:58:09Z","timestamp":1778702289900,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Animal models are essential to study novel antiretroviral drugs, resistance-associated mutations (RAMs), and treatment strategies. Bictegravir (BIC) is a novel potent integrase strand transfer inhibitor (INSTI) that has shown promising results against HIV-1 infection\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            and against clinical isolates with resistance against INSTIs. BIC has a higher genetic barrier to the development of resistance than two clinically approved INSTIs, termed raltegravir and elvitegravir. Another clinically approved INSTI, dolutegravir (DTG) also possesses a high genetic barrier to resistance, while a fourth compound, termed cabotegravir (CAB), is currently in late phases of clinical development. Here we report the susceptibilities of simian immunodeficiency virus (SIV) and HIV-1 integrase (IN) mutants containing various RAMs to BIC, CAB, and DTG. BIC potently inhibited SIV and HIV-1 in single cycle infection with 50% effective concentrations (EC\n            <jats:sub>50<\/jats:sub>\n            s) in the low nM range. In single cycle SIV infections, none of the E92Q, T97A, Y143R, or N155H substitutions had a significant effect on susceptibility to BIC (\u22644-fold increase in EC\n            <jats:sub>50<\/jats:sub>\n            ), whereas G118R and R263K conferred \u223c14-fold and \u223c6-fold increases in EC\n            <jats:sub>50<\/jats:sub>\n            , respectively. In both single and multiple rounds of HIV-1 infections, BIC remained active against the Y143R, N155H, R263K, R263K\/M50I, and R263K\/E138K mutants (\u22644-fold increase in EC\n            <jats:sub>50<\/jats:sub>\n            ). In multiple rounds of infection, the G140S\/Q148H combination of substitutions decreased HIV-1 susceptibility to BIC 4.8-fold compared to 16.8- and 7.4-fold for CAB and DTG, respectively. BIC possesses an excellent resistance profile in regard to HIV and SIV and could be useful in nonhuman primate models of HIV infection.\n          <\/jats:p>","DOI":"10.1128\/aac.01695-17","type":"journal-article","created":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T00:40:23Z","timestamp":1505781623000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1"],"prefix":"10.1128","volume":"61","author":[{"given":"Said A.","family":"Hassounah","sequence":"first","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Experimental Medicine, Faculty of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Alikhani","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Oliveira","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simrat","family":"Bharaj","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxandra-Ilinca","family":"Ibanescu","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Osman","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Tao","family":"Xu","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bluma G.","family":"Brenner","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-9128","authenticated-orcid":false,"given":"Thibault","family":"Mespl\u00e8de","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Wainberg","sequence":"additional","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Experimental Medicine, Faculty of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, 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