{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:07:13Z","timestamp":1760299633798,"version":"3.27.0"},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T00:00:00Z","timestamp":1509321600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T00:00:00Z","timestamp":1509321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{},{},{}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>People with hepatitis C virus (HCV) infection who have failed treatment with an all\u2010oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor\u2010containing regimen. C\u2010SURGE (PN\u20103682\u2010021) and C\u2010CREST Part C (PN\u20103682\u2010011 and \u2010012) were open\u2010label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor\u2013containing all\u2010oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was sustained virologic response (HCV RNA below the limit of quantitation [&lt;15 IU\/mL]) 12 weeks after treatment completion (SVR12). In C\u2010SURGE, SVR12 was achieved by 49\/49 (100%) and 43\/44 (98%) genotype (GT)1 participants in the 24\u2010week no ribavirin arm and the 16\u2010week plus ribavirin arm (lost to follow\u2010up, n = 1), respectively. In C\u2010CREST Part C, SVR12 was achieved by 23\/24 (96%) participants treated for 16 weeks with ribavirin (GT1, 2\/2 [100%]; GT2, 13\/14 [93%]; GT3, 8\/8 [100%]). One participant with GT2 infection discontinued study medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus ribavirin due to serious adverse events of vomiting and tachycardia. The presence of baseline resistance\u2010associated substitutions had no impact on SVR12. No participant who completed treatment in either study experienced virologic failure. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor\u2013containing therapy. (H<jats:sc>epatology<\/jats:sc> 2017;66:1794\u20131804)<\/jats:p>","DOI":"10.1002\/hep.29358","type":"journal-article","created":{"date-parts":[[2017,7,8]],"date-time":"2017-07-08T04:56:44Z","timestamp":1499489804000},"page":"1794-1804","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":24,"title":["Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure"],"prefix":"10.1097","volume":"66","author":[{"given":"David","family":"Wyles","sequence":"first","affiliation":[{"name":"University of Colorado School of Medicine,Denver,CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziv","family":"Ben\u2010Ari","sequence":"additional","affiliation":[{"name":"Sheba Medical Center,Tel Hashomer,Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Gane","sequence":"additional","affiliation":[{"name":"Auckland Hospital,Auckland,New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper Bach","family":"Hansen","sequence":"additional","affiliation":[{"name":"Aalborg University Hospital, Department of Gastroenterology,Aalborg,Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ira M.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex L.","family":"Laursen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,Aarhus University Hospital,Skejby,Aarhus,Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Luetkemeyer","sequence":"additional","affiliation":[{"name":"Zuckerberg San Francisco General Hospital,University of California San Francisco,San Francisco,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Nahass","sequence":"additional","affiliation":[{"name":"ID Care,Hillsborough,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Pianko","sequence":"additional","affiliation":[{"name":"Monash Medical Centre,Clayton,Victoria,Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Goethe University Hospital,Frankfurt,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Jumes","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueh\u2010Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Butterton","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Robertson","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Wahl","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliav","family":"Barr","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee\u2010Koung","family":"Joeng","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Martin","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.,Kenilworth,NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Serfaty","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9patologie, H\u00f4pital Saint\u2010Antoine,Universit\u00e9 Pierre & Marie Curie,Paris,France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the C\u2010CREST Part C and C\u2010SURGE Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2017,10,30]]},"reference":[{"key":"hep29358-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.jhep.2016.11.022","article-title":"Post\u2010treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir\/sofosbuvir","volume":"66","year":"2017","journal-title":"J Hepatol"},{"issue":"suppl. 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