{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:21:52Z","timestamp":1776291712213,"version":"3.50.1"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Agence Nationale de Recherche sur le SIDA et les h\u00e9patites virales (ANRS) | Maladies Infectieuses Emergentes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>HIV-2 resistance to integrase strand-transfer inhibitors (INSTIs) is characterized by two main pathways: (i) mutations at codons 143, 148 and155; and (ii) amino acid insertion after integrase codon 231 (231ins).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To complete INSTI resistance data on HIV-2 by determining the viral replicative capacity and INSTI phenotypic susceptibility of integrase mutants obtained through site-directed mutagenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Site-directed mutants (SDMs) were constructed and viral stocks produced. Viral replicative capacity was assessed by measuring HIV-2 viral load at days 3, 7 and 14. In vitro phenotypic susceptibility was measured using the ANRS PBMC assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Viruses bearing 231ins did not present impaired replicative capacity, except the 231ins GIRGK mutant. A 231ins GK SDM was resistant to raltegravir and cabotegravir, but remained susceptible to dolutegravir and bictegravir. SDMs harbouring a 5 amino acid insertion (GYKGK or SREGK) were both resistant to all INSTIs. The SDM with T97A+N155H, with or without E92Q, was resistant to all INSTIs, except bictegravir.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These first data on the newly described resistance pathway 231ins, using site-directed mutagenesis, showed no measurable impact on viral fitness and confirmed the decreased susceptibility to a first-generation INSTI (raltegravir) and cabotegravir. Resistance to second-generation INSTIs (dolutegravir and bictegravir) occurred for mutants with a 5 amino acid 231ins.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab387","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T11:08:44Z","timestamp":1635419324000},"page":"409-412","source":"Crossref","is-referenced-by-count":4,"title":["<i>In vitro<\/i> analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions"],"prefix":"10.1093","volume":"77","author":[{"given":"Quentin","family":"Le Hingrat","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Collin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Damond","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4359-537X","authenticated-orcid":false,"given":"Gilles","family":"Peytavin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM UMR 1137 IAME, Laboratoire de Pharmacologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Lebourgeois","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jade","family":"Ghosn","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM UMR 1137 IAME, Service de Maladies Infectieuses et Tropicales, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Bachelard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM UMR 1137 IAME, Service de Maladies Infectieuses et Tropicales, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentine Marie","family":"Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Matheron","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM UMR 1137 IAME, Service de Maladies Infectieuses et Tropicales, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Descamps","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Charpentier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IAME, UMR 1137, Service de Virologie, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, 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