{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T08:17:57Z","timestamp":1772612277154,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T00:00:00Z","timestamp":1542758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]},{"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\/100007054","name":"Meso Scale Diagnostics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011699","name":"Siemens Healthineers","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of the study was to analyse the prevalence of integrase resistance mutations in integrase strand transfer inhibitor (<jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>)\u2010experienced <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101\u2010infected patients and its predictors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 integrase sequences from the Antiviral Response Cohort Analysis (<jats:styled-content style=\"fixed-case\">ARCA<\/jats:styled-content>) database, derived from <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>\u2010experienced patients between 2008 and 2017. Differences in the prevalence of resistance to raltegravir (<jats:styled-content style=\"fixed-case\">RAL<\/jats:styled-content>), elvitegravir (<jats:styled-content style=\"fixed-case\">EVG<\/jats:styled-content>) and dolutegravir (<jats:styled-content style=\"fixed-case\">DTG<\/jats:styled-content>) were assessed by \u03c7<jats:sup>2<\/jats:sup> test and predictors of resistance were analysed by logistic regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 462 genotypes from <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>\u2010exposed individuals: 356 \u2018<jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>\u2010failing' patients and 106 \u2018previously <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>\u2010exposed' patients (obtained a median of 42 weeks after INSTI discontinuation [interquartile range (<jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content>) 17\u2013110 weeks]). Overall, at least low\u2010level resistance (<jats:styled-content style=\"fixed-case\">LLR<\/jats:styled-content>) to any <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content> (Stanford 8.5 algorithm) was detected in 198 (42.9%) cases. The most frequent <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content> resistance mutation was N155H, followed by Q148H\/K\/R, G140A\/C\/S, E138A\/K\/T and Y143C\/H\/R. Y143R and E138A were more prevalent in viral subtype B versus non\u2010B [5.2 versus 1.5%, respectively (<jats:italic>P<\/jats:italic> = 0.04), and 3.1 versus 0%, respectively (<jats:italic>P<\/jats:italic> = 0.02)]. Overall, the Q148H\/K\/R plus G140A\/C\/S and\/or E138A\/K\/T pattern, defining an intermediate level of resistance to <jats:styled-content style=\"fixed-case\">DTG<\/jats:styled-content>, was detected in 70 (15%) cases. Independent predictors of at least <jats:styled-content style=\"fixed-case\">LLR<\/jats:styled-content> to any <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content> were current use versus past use of <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>s, a lower genotypic sensitivity score (<jats:styled-content style=\"fixed-case\">GSS<\/jats:styled-content>) for contemporary antiretroviral drugs used, and having an integrase sequence obtained in calendar year 2016 as compared to 2008\u20132009.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results support integrase resistance testing in <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content>\u2010experienced patients. Emergence of <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content> resistance is facilitated by the reduced genetic barrier of the regimen as a consequence of resistance to companion drugs. However, <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content> resistance may become undetectable by standard population sequencing upon <jats:styled-content style=\"fixed-case\">INSTI<\/jats:styled-content> discontinuation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.12692","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T13:45:57Z","timestamp":1542807957000},"page":"137-146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Prevalence and determinants of resistance mutations in <scp>HIV<\/scp>\u20101\u2010infected patients exposed to integrase inhibitors in a large Italian cohort"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7940-1370","authenticated-orcid":false,"given":"S","family":"Modica","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit Siena University Hospital Siena Italy"},{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-9241","authenticated-orcid":false,"given":"B","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit Siena University Hospital Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Institute of Clinical Infectious Diseases Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Lagi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Maffeo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit Siena University Hospital Siena Italy"},{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"D'Autilia","sequence":"additional","affiliation":[{"name":"Department of Mathematics University of Roma Tre Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Pecorari","sequence":"additional","affiliation":[{"name":"Unit of Microbiology and Virology Modena University Hospital Modena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Vicenti","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Bruzzone","sequence":"additional","affiliation":[{"name":"Hygiene Unit Policlinico San Martino Hospital Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Magnani","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases S. 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