{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T19:59:16Z","timestamp":1760385556953},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2017,10]]},"abstract":"Summary<\/jats:title>Elbasvir (EBR<\/jats:styled-content>; HCV NS<\/jats:styled-content>5A inhibitor) and grazoprevir (GZR<\/jats:styled-content>; HCV NS<\/jats:styled-content>3\/4A protease inhibitor) are approved as a fixed\u2010dose combination to treat patients chronically infected with HCV<\/jats:styled-content> genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR<\/jats:styled-content>+GZR<\/jats:styled-content> was assessed in HCV GT<\/jats:styled-content>3\u2010infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18\u00a0weeks of EBR<\/jats:styled-content>+GZR<\/jats:styled-content> with ribavirin (RBV<\/jats:styled-content>) in treatment\u2010na\u00efve, noncirrhotic HCV GT<\/jats:styled-content>3\u2010infected patients. Randomized patients received open\u2010label EBR<\/jats:styled-content> (50\u00a0mg once daily) + GZR<\/jats:styled-content> (100\u00a0mg once daily) + RBV<\/jats:styled-content>. The primary efficacy objective was to evaluate the sustained virologic response rates 12\u00a0weeks after the end of all study therapy (SVR<\/jats:styled-content>12). SVR<\/jats:styled-content>12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR<\/jats:styled-content>+GZR<\/jats:styled-content>+RBV<\/jats:styled-content> for 12\u00a0weeks or 18\u00a0weeks, respectively. On\u2010treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance\u2010associated substitutions (RAS<\/jats:styled-content>s) with a >five\u2010fold shift in potency occurred in the NS<\/jats:styled-content>3 region in six (35%) patients and in the NS<\/jats:styled-content>5A region in 16 (94%) patients. The most common RAS<\/jats:styled-content> at virologic failure was Y93H in NS<\/jats:styled-content>5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR<\/jats:styled-content>+GZR<\/jats:styled-content>+RBV<\/jats:styled-content> was suboptimal in HCV GT<\/jats:styled-content>3\u2010infected patients due to a high rate of on\u2010treatment virologic failure and treatment\u2010emergent RAS<\/jats:styled-content>s which demonstrates an inadequate barrier to the development of GT<\/jats:styled-content>3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR<\/jats:styled-content>+GZR<\/jats:styled-content>+RBV<\/jats:styled-content> in GT<\/jats:styled-content>3\u2010infected patients.clinicaltrials.gov: NCT01717326.<\/jats:p>","DOI":"10.1111\/jvh.12719","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T09:02:45Z","timestamp":1493888565000},"page":"895-899","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy of 12 or 18\u00a0weeks of elbasvir plus grazoprevir with ribavirin in treatment\u2010na\u00efve, noncirrhotic HCV<\/scp> genotype 3\u2010infected patients"],"prefix":"10.1111","volume":"24","author":[{"given":"E.","family":"Gane","sequence":"first","affiliation":[{"name":"Auckland Clinical Studies Grafton Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Nahass","sequence":"additional","affiliation":[{"name":"ID Care Hillsborough NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Luketic","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition Virginia Commonwealth University School of Medicine Richmond VA USA"},{"name":"Hunter Holmes McGuire Department of Veterans Affairs Medical Center Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Asante\u2010Appiah","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Hwang","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Wahl","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Barr","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Haber","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. 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