{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:13:51Z","timestamp":1778314431025,"version":"3.51.4"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:00:00Z","timestamp":1493683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fonds de Recherche du Qu\u00e9bec"},{"name":"R\u00e9seau SIDA and FRQ\/Research Foundation Flanders","award":["202685"],"award-info":[{"award-number":["202685"]}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["HIV142"],"award-info":[{"award-number":["HIV142"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008136","name":"Case Western Reserve University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008136","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"}]},{"name":"University Hospitals Cleveland Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Objectives: Viral phylogenetics revealed two patterns of HIV-1 spread among MSM in Quebec. While most HIV-1 strains (n\u2009=\u20092011) were associated with singleton\/small clusters (cluster size 1\u20134), 30 viral lineages formed large networks (cluster size 20\u2013140), contributing to 42% of diagnoses between 2011 and 2015. Herein, tissue culture selections ascertained if large cluster lineages possessed higher replicative fitness than singleton\/small cluster isolates, allowing for viral escape from integrase inhibitors.<\/jats:p><jats:p>Methods: Primary HIV-1 isolates from large 20+ cluster (n\u2009=\u200911) or singleton\/small cluster (n\u2009=\u20096) networks were passagedin vitro in escalating concentrations of dolutegravir, elvitegravir and lamivudine for 24\u201336\u2009weeks. Sanger and deep sequencing assessed genotypic changes under selective drug pressure.<\/jats:p><jats:p>Results: Large cluster HIV-1 isolates selected for resistance to dolutegravir, elvitegravir and lamivudine faster than HIV-1 strains forming small clusters. With dolutegravir, large cluster HIV-1 variants acquired solitary R263K (n\u2009=\u20097), S153Y (n\u2009=\u20091) or H51Y (n\u2009=\u20091) mutations as the dominant quasi-species within 8\u201312\u2009weeks as compared with small cluster lineages where R263K (n\u2009=\u20091\/6), S153Y (1\/6) or WT species (4\/6) were observed after 24\u2009weeks. Interestingly, dolutegravir-associated mutations compromised viral replicative fitness, precluding escalations in concentrations beyond 5\u201310\u2009nM. With elvitegravir, large cluster variants more rapidly acquired first mutations (T66I, A92G, N155H or S147G) by week 8 followed by sequential accumulation of multiple mutations leading to viral escape (&amp;gt;10\u2009\u03bcM) by week 24.<\/jats:p><jats:p>Conclusions: Further studies are needed to understand virological features of large cluster viruses that may favour their transmissibility, replicative competence and potential to escape selective antiretroviral drug pressure.<\/jats:p>","DOI":"10.1093\/jac\/dkx118","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T11:38:03Z","timestamp":1490701083000},"page":"2171-2183","source":"Crossref","is-referenced-by-count":12,"title":["HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton\/small clusters"],"prefix":"10.1093","volume":"72","author":[{"given":"Bluma G.","family":"Brenner","sequence":"first","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxandra-Ilinca","family":"Ibanescu","sequence":"first","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Oliveira","sequence":"first","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Roger","sequence":"first","affiliation":[{"name":"D\u00e9partement de Microbiologie et d\u2019Immunologie et Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Hardy","sequence":"first","affiliation":[{"name":"D\u00e9partement de Microbiologie et d\u2019Immunologie et Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"Routy","sequence":"first","affiliation":[{"name":"Centre hospitalier de l\u2019Universit\u00e9 McGill, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Kyeyune","sequence":"first","affiliation":[{"name":"Departments of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel E.","family":"Qui\u00f1ones-Mateu","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, OH, USA"},{"name":"University Hospitals Translational Laboratory, University Hospitals Cleveland Medical Center, Cleveland, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Wainberg","sequence":"first","affiliation":[{"name":"McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Montreal PHI Cohort Study Group","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,5,2]]},"reference":[{"key":"2020060116200416700_dkx118-B1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/S0140-6736(10)60936-1","article-title":"Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British 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