{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:13:22Z","timestamp":1778314402564,"version":"3.51.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"internal funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24\u2009weeks. Our objective was to study the effects of these substitutions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa471","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T19:12:01Z","timestamp":1603480321000},"page":"639-647","source":"Crossref","is-referenced-by-count":12,"title":["Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir"],"prefix":"10.1093","volume":"76","author":[{"given":"Hanh T","family":"Pham","sequence":"first","affiliation":[{"name":"McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 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":"Brunna M","family":"Alves","sequence":"additional","affiliation":[{"name":"Programa de Oncovirologia, Instituto Nacional de C\u00e2ncer, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunbin","family":"Yoo","sequence":"additional","affiliation":[{"name":"McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 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":"Meng A","family":"Xiao","sequence":"additional","affiliation":[{"name":"McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 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":"Jing","family":"Leng","sequence":"additional","affiliation":[{"name":"McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 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":"Peter K","family":"Quashie","sequence":"additional","affiliation":[{"name":"West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana"},{"name":"The Francis Crick Institute, London, UK"},{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esmeralda A","family":"Soares","sequence":"additional","affiliation":[{"name":"Programa de Oncovirologia, Instituto Nacional de C\u00e2ncer, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"Routy","sequence":"additional","affiliation":[{"name":"For Montreal PHI Cohort Study Group, Division of Hematology, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo A","family":"Soares","sequence":"additional","affiliation":[{"name":"Programa de Oncovirologia, Instituto Nacional de C\u00e2ncer, Rio de Janeiro, Brazil"},{"name":"Departamento de Gen\u00e9tica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thibault","family":"Mespl\u00e8de","sequence":"additional","affiliation":[{"name":"McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 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"}]}],"member":"286","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"2021021208581055700_dkaa471-B1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1001\/jama.2018.8431","article-title":"Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society-USA Panel","volume":"320","author":"Saag","year":"2018","journal-title":"JAMA"},{"key":"2021021208581055700_dkaa471-B2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3109\/07853890.2014.883169","article-title":"Integrase strand transfer inhibitors in the management of HIV-positive individuals","volume":"46","author":"Mesplede","year":"2014","journal-title":"Ann Med"},{"key":"2021021208581055700_dkaa471-B3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/14656566.2018.1560423","article-title":"Bictegravir 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