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Sanger sequencing of NS3\/NS5A\/NS5B was performed following home\u2010made protocols.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co\u2010infected. Phylogenetic analysis classified sequences as GT3a\u2010b\u2010g\u2010h (98%\u20100.4%\u20100.2%\u20101.2%) respectively.<\/jats:p><jats:p>Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)\/daclatasvir (DCV) or velpatasvir (VEL)\u00b1ribavirin (RBV) (N\u00a0=\u00a091\/15) and glecaprevir (G)\/pibrentasvir (P) (N\u00a0=\u00a09). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D\u00a0\u00b1\u00a0RBV (Paritaprevir\/r\u00a0+\u00a0Ombitasvir+Dasabuvir, N\u00a0=\u00a015), SOF\u00a0+\u00a0Simeprevir (SIM) (N\u00a0=\u00a01) or SOF\/Ledipasvir (LDV)\u00a0\u00b1\u00a0RBV (N\u00a0=\u00a04).<\/jats:p><jats:p>RAS prevalence was 15.8% in DAA\u2010na\u00efve patients. At failure, 81.5% patients showed at least one RAS: 11\/25 (44.0%) in NS3, 109\/135 (80.7%) in NS5A, 7\/111 (6.3%) in NS5B SOF\u2010failures. In NS5A\u2010failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA\u2010na\u00efve, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) followed by A30K (12.7% vs 2.8% in DAA\u2010na\u00efve, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Analysing baseline samples, a higher prevalence of NS5A\u2010RASs was observed before treatment in DAA\u2010failures (5\/13, 38.5%) vs DAA\u2010na\u00efves (61\/393, 15.5%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.04). Regarding 228 DAA\u2010na\u00efve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and\/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A\u2010RASs (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this real\u2010life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A\u2010RASs, the most frequent being Y93H. The presence of natural NS5A\u2010RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14797","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T15:17:53Z","timestamp":1611674273000},"page":"1802-1814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Resistance analysis and treatment outcomes in hepatitis C virus genotype 3\u2010infected patients within the Italian network VIRONET\u2010C"],"prefix":"10.1111","volume":"41","author":[{"given":"Velia Chiara","family":"Di Maio","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Barbaliscia","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Teti","sequence":"additional","affiliation":[{"name":"Infectious Diseases University Hospital of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Infectious Diseases Sant\u2019Andrea Hospital \u2013 \u201cLa Sapienza\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Milana","sequence":"additional","affiliation":[{"name":"Hepatology Unit University Hospital of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Paolucci","sequence":"additional","affiliation":[{"name":"Molecular Virology Unit, Microbiology and Virology Department IRCCS Policlinic Foundation San Matteo Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-3035","authenticated-orcid":false,"given":"Teresa","family":"Pollicino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University Hospital of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-5376","authenticated-orcid":false,"given":"Giulia","family":"Morsica","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases IRCCS, Ospedale San Raffaele Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Starace","sequence":"additional","affiliation":[{"name":"Laboratory for the identification of prognostic factors of response to the treatment against infectious diseases University of Campania \"L. 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