{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:16:20Z","timestamp":1783948580424,"version":"3.55.0"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016145","name":"Ministerio de Sanidad, Consumo y Bienestar Social","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016145","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001872","name":"Centro para el Desarrollo Tecnol\u00f3gico Industrial","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001872","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Direct\u2010acting antivirals (DAAs) resolve chronic HCV infection in &gt;95% of patients, but a small percentage do not respond to DAA\u2010based therapy. These may be difficult to treat because of resistance\u2010associated substitutions (RAS) emerging after treatment failure. Triple therapy with sofosbuvir (SOF)\/velpatasvir (VEL)\/voxilaprevir (VOX) is the recommended retreatment after DAA\u2010based failure. However, in rare cases, failure to triple therapy occurs, and there is little information characterizing the viruses that relapse. To determine the RAS profile after failing SOF\/VEL\/VOX, and seek suitable alternatives for retreatment, samples from 5 patients were analysed using MiSeq Illumina deep sequencing before and after triple therapy. All patients were men, aged 59\u201378\u00a0years, 2 HCV genotype (G) 1b and 3 G3a. The most prevalent NS3 substitutions after SOF\/VEL\/VOX failure were Y56F and A166T. Four patients had the NS5A RAS, Y93H, after triple failure, and Y93H was observed in both G1b patients before retreatment and after SOF\/ledipasvir failure. In 2 G3a patients, Y93H appeared at triple failure, and on the other G3a, A30K persisted in 100% of viral genomes. Finally, G1b patients showed C316N in NS5B, associated with SOF failure, but G3a patients had no known NS5B substitutions. HCV RAS analysis identified the following substitutions present at higher rates after triple failure: Y56F in NS3 (G1b), A166T in NS3 (G3a), A30K or Y93H in NS5A, and C316N in NS5B (G1b). A RAS\u2010based salvage treatment (SOF\u00a0+\u00a0glecaprevir\/pibrentasvir\u00a0+\u00a0RBV) was successfully used in one G3a patient.<\/jats:p>","DOI":"10.1111\/jvh.13497","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T13:21:24Z","timestamp":1615814484000},"page":"1319-1324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Resistance\u2010associated substitutions after sofosbuvir\/velpatasvir\/voxilaprevir triple therapy failure"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-038X","authenticated-orcid":false,"given":"Damir","family":"Garcia\u2010Cehic","sequence":"first","affiliation":[{"name":"Liver Diseases\u2010Viral Hepatitis Liver Unit Vall d\u2019Hebron Institut de Recerca (VHIR) Vall d\u2019Hebron Hospital Universitari Vall d\u2019Hebron Barcelona Hospital Campus Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4555-7286","authenticated-orcid":false,"given":"Ariadna","family":"Rando","sequence":"additional","affiliation":[{"name":"Biochemistry and Microbiology Departments Vall d\u2019Hebron Institut de Recerca (VHIR Vall d\u2019Hebron Hospital Universitari Vall d\u2019Hebron Barcelona Hospital Campus Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-7013","authenticated-orcid":false,"given":"Francisco","family":"Rodriguez\u2010Frias","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd Instituto de Salud Carlos III Madrid Spain"},{"name":"Biochemistry and Microbiology Departments Vall d\u2019Hebron Institut de Recerca (VHIR Vall d\u2019Hebron Hospital Universitari Vall d\u2019Hebron Barcelona Hospital Campus Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona Bellaterra, Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4253-8015","authenticated-orcid":false,"given":"Josep","family":"Gregori","sequence":"additional","affiliation":[{"name":"Liver Diseases\u2010Viral Hepatitis Liver Unit Vall d\u2019Hebron Institut de Recerca (VHIR) Vall d\u2019Hebron Hospital Universitari Vall d\u2019Hebron Barcelona Hospital Campus Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd Instituto de Salud Carlos III Madrid Spain"},{"name":"Roche Diagnostics SL Sant Cugat del Vall\u00e8s Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-7432","authenticated-orcid":false,"given":"Juan Garcia","family":"Costa","sequence":"additional","affiliation":[{"name":"Virology and Molecular Biology Unit Microbiology Department Complexo Hospitalario Universitario de Ourense (CHUO) Ourense Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-6081","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Carri\u00f3n","sequence":"additional","affiliation":[{"name":"Liver Section Gastroenterology Department Hospital del Mar Parc de Salur Mar Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro","family":"Macenlle","sequence":"additional","affiliation":[{"name":"Virology and Molecular Biology Unit Microbiology Department Complexo Hospitalario Universitario de Ourense (CHUO) Ourense Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2922-1603","authenticated-orcid":false,"given":"Javier","family":"Pamplona","sequence":"additional","affiliation":[{"name":"Gastroenterology Department Hospital de Santa Caterina Salt. 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