{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T20:03:39Z","timestamp":1760385819780,"version":"3.40.5"},"reference-count":10,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first\u2010line integrase strand transfer inhibitor (InSTI)\u2010based regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients starting two NRTIs (lamivudine\/emtricitabine plus abacavir\/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads &gt;\u00a050 HIV\u20101 RNA copies\/mL or a single viral load \u2265\u00a0200 copies\/mL after 3\u00a0months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39\u00a0years). In all, 207 VFs occurred over 1023 patient\u2010years of follow\u2010up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V\/I independently predicted VF of raltegravir\u2010 but not dolutegravir\u2010based therapy when compared with a fully\u2010active backbone [adjusted hazard ratio (aHR) = 3.09, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.035], particularly when associated with other non\u2010thymidine analogue mutations (aHR = 27.62, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004). Higher\u2010zenith HIV\u2010RNA and lower nadir CD4 counts independently predicted VF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NRTI backbone TDRMs increased the risk of VF with raltegravir\u2010based but not dolutegravir\u2010based regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.12956","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T09:37:14Z","timestamp":1600853834000},"page":"22-27","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Transmitted drug resistance to NRTIs and risk of virological failure in na\u00efve patients treated with integrase inhibitors"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7910-021X","authenticated-orcid":false,"given":"A","family":"Borghetti","sequence":"first","affiliation":[{"name":"UOC Malattie Infettive Fondazione Policlinico Universitario A. Gemelli IRCCS Roma Italia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-883X","authenticated-orcid":false,"given":"A","family":"Ciccullo","sequence":"additional","affiliation":[{"name":"Istituto Clinica Malattie Infettive Universit\u00e0 Cattolica del Sacro Cuore Roma Italia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Istituto Clinica Malattie Infettive Universit\u00e0 Cattolica del Sacro Cuore Roma Italia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-9976","authenticated-orcid":false,"given":"G","family":"Baldin","sequence":"additional","affiliation":[{"name":"Istituto Clinica Malattie Infettive Universit\u00e0 Cattolica del Sacro Cuore Roma Italia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-6652","authenticated-orcid":false,"given":"S","family":"Belmonti","sequence":"additional","affiliation":[{"name":"Istituto Clinica Malattie Infettive Universit\u00e0 Cattolica del Sacro Cuore Roma Italia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Prosperi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Florida Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Incardona","sequence":"additional","affiliation":[{"name":"EuResist Network Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Heger","sequence":"additional","affiliation":[{"name":"Institute of Virology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Borghi","sequence":"additional","affiliation":[{"name":"Clinica delle Malattie Infettive e Tropicali dell'Universit\u00e0 di Modena e Reggio Emilia Modena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"S\u00f6nnerborg","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Medicine Huddinge Karolinska Institutet Karolinska University Hospital Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Zazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology University of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"De Luca","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit Siena University Hospital Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Di Giambenedetto","sequence":"additional","affiliation":[{"name":"UOC Malattie Infettive Fondazione Policlinico Universitario A. Gemelli IRCCS Roma Italia"},{"name":"Istituto Clinica Malattie Infettive Universit\u00e0 Cattolica del Sacro Cuore Roma Italia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"unstructured":"Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Available athttps:\/\/aidsinfo.nih.gov\/guidelines(accessed 2 March 2019).","key":"e_1_2_8_2_1"},{"unstructured":"EACS Guidelines Version 10.0 November 2019.","key":"e_1_2_8_3_1"},{"issue":"9","key":"e_1_2_8_4_1","first-page":"2480","article-title":"Impact of transmitted HIV\u20101 drug resistance on the efficacy of first\u2010line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor","volume":"73","author":"Spertilli R","year":"2018","journal-title":"J AntimicrobChemother"},{"volume-title":"DTG\u2010based regimens are active in INI\u2010naive patients with a history of NRTI resistance","year":"2014","author":"Demarest J","key":"e_1_2_8_5_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_6_1","DOI":"10.1016\/S1473-3099(19)30036-2"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1086\/503914"},{"issue":"4","key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.5582\/bst.2017.01194","article-title":"Latest advances in the efficacy, tolerability, and monotherapy of integrase inhibitors","volume":"11","author":"Tang Q","year":"2017","journal-title":"BioScience Trends"},{"issue":"7","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.3851\/IMP2531","article-title":"Impact of pre\u2010therapy viral load on virological response to modern first\u2010line HAART","volume":"18","author":"Santoro MM","year":"2013","journal-title":"Antivir Ther"},{"doi-asserted-by":"publisher","key":"e_1_2_8_10_1","DOI":"10.1016\/S0140-6736(14)61170-3"},{"doi-asserted-by":"publisher","key":"e_1_2_8_11_1","DOI":"10.1097\/00042560-200107010-00006"}],"container-title":["HIV Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hiv.12956","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hiv.12956","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hiv.12956","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T23:34:11Z","timestamp":1693870451000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hiv.12956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,23]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/hiv.12956"],"URL":"https:\/\/doi.org\/10.1111\/hiv.12956","archive":["Portico"],"relation":{},"ISSN":["1464-2662","1468-1293"],"issn-type":[{"type":"print","value":"1464-2662"},{"type":"electronic","value":"1468-1293"}],"subject":[],"published":{"date-parts":[[2020,9,23]]},"assertion":[{"value":"2020-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}