{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:37:14Z","timestamp":1790613434267,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,1,20]],"date-time":"2019-01-20T00:00:00Z","timestamp":1547942400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern AIDS Soc"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Concerns about dolutegravir (DTG) tolerability in the real\u2010life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG\u2010based regimens from a large cohort of HIV\u2010infected individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a multicentre, observational study including all antiretroviral therapy (ART)\u2010na\u00efve and virologically suppressed treatment\u2010experienced (TE) patients from the Icona (Italian Cohort Na\u00efve Antiretrovirals) cohort who started, for the first time, a DTG\u2010based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan\u2013Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>About 1679 individuals (932 ART\u2010na\u00efve, 747 TE) were included. The one\u2010 and two\u2010year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART\u2010na\u00efve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART\u2010na\u00efve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART\u2010na\u00efve (2.1%) and TE (1.7%) patients. In ART\u2010na\u00efve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH)\u00a0=\u00a03.38, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH\u00a0=\u00a03.30, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.009). TE patients starting a DTG\u2010based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR)\u00a0=\u00a02.50, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.037 for ABC\u2010based triple\u2010therapies, aHR\u00a0=\u00a03.56, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.012 for tenofovir\u2010based) and for toxicity (aHR\u00a0=\u00a05.26, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.030 for ABC\u2010based, aHR\u00a0=\u00a06.60, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.024 for tenofovir\u2010based). The one\u2010 and two\u2010year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART na\u00efve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first\u2010line and switching ART. The low risk of treatment\u2010limiting toxicities in ART\u2010na\u00efve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25227","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T07:29:53Z","timestamp":1548055793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Effectiveness of dolutegravir\u2010based regimens as either first\u2010line or switch antiretroviral therapy: data from the Icona cohort"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-2610","authenticated-orcid":false,"given":"Annalisa","family":"Mondi","sequence":"first","affiliation":[{"name":"HIV\/AIDS Department National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cozzi\u2010Lepri","sequence":"additional","affiliation":[{"name":"Institute for Global Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Tavelli","sequence":"additional","affiliation":[{"name":"Icona Foundation Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Rusconi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit ASST FBF\u2010Sacco, DIBIC \u201cL. Sacco\u201d University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vichi","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Santa Maria Annunziata Hospital Firenze Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ceccherini\u2010Silberstein","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Surgery University of Rome Tor Vergata Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Calcagno","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Medical Sciences Amedeo di Savoia Hospital University of Torino Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"De Luca","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Maggiolo","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases ASST\u2010PG23 Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Clinic of Infectious and Tropical Diseases Department of Health Sciences ASST Santi Paolo e Carlo University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Department National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"d'Arminio Monforte","sequence":"additional","affiliation":[{"name":"Clinic of Infectious and Tropical Diseases Department of Health Sciences ASST Santi Paolo e Carlo University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Icona Foundation Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,20]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Panel\u00a0on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents.Department of Health and Human Services;2017. 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