{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:36:02Z","timestamp":1778679362156,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In HCV-infected people who fail to achieve sustained virological response after receiving a direct-acting antiviral regimen, virological failure is almost always accompanied by the presence of resistance-associated substitutions (RASs) in the target protein(s). The aim of this long-term observational study was to evaluate the persistence of NS3\/4A and NS5A RASs in participants with genotype (GT) 1 infection who relapsed following treatment with a grazoprevir-containing treatment regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RASs were evaluated at baseline (that is, pre-dose on day 1 of the original treatment), at the time of virological failure, and up to follow-up week 96. A total of 58 participants were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In participants treated with elbasvir\/grazoprevir \u00b1 ribavirin, observed baseline NS3 RASs included 56F, 80K\/L, 122N and 170V\/I, and observed treatment-emergent NS3 RASs included 36M, 56F\/H, 122G, 132I, 156G\/I\/L\/P\/T, 168A\/E\/G\/V\/Y and 170T. Observed baseline NS5A RASs included 28M\/T\/V, 30H\/R, 31M\/V and 93H\/N, and treatment-emergent NS5A RASs included 28A\/G\/S\/T, 30H\/R, 31M\/V and 93H\/N\/S. Baseline NS3 and NS5A RASs present at time of failure tended to persist during follow-up, and most were detectable for more than 2 years following virological failure. Treatment-emergent NS5A RASs present at time of failure also tended to persist for more than 2 years following virological failure (93%). By contrast, &gt;80% of treatment-emergent NS3 RASs detected at failure had been supplanted by wild type by week 36.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment-emergent NS5A RASs can persist for extended periods of time. Retreatment strategies should take account of the presence of these RASs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3253","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T04:15:56Z","timestamp":1532405756000},"page":"593-603","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Interim analysis of a 3-year follow-up study of NS5A and NS3 resistance-associated substitutions after treatment with grazoprevir-containing regimens in participants with chronic HCV infection"],"prefix":"10.1177","volume":"23","author":[{"given":"Frederick","family":"Lahser","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Galloway","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peggy","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Palcza","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joann","family":"Brunhofer","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Wahl","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliav","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest","family":"Asante-Appiah","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Haber","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Merck & Co., Inc. Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,10,1]]},"reference":[{"key":"bibr1-IMP3253","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.04.003"},{"key":"bibr2-IMP3253","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25048"},{"key":"bibr3-IMP3253","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29837"},{"key":"bibr4-IMP3253","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1050"},{"key":"bibr5-IMP3253","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02929-15"},{"key":"bibr6-IMP3253","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02494-12"},{"key":"bibr7-IMP3253","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.10.010"},{"key":"bibr8-IMP3253","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.12.015"},{"key":"bibr9-IMP3253","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.02.017"},{"key":"bibr10-IMP3253","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00324-12"},{"key":"bibr11-IMP3253","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201300343"},{"key":"bibr12-IMP3253","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00051-16"},{"key":"bibr13-IMP3253","doi-asserted-by":"publisher","DOI":"10.7326\/M15-0785"},{"key":"bibr14-IMP3253","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.09.045"},{"key":"bibr15-IMP3253","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.04.009"},{"key":"bibr16-IMP3253","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00114-9"},{"key":"bibr17-IMP3253","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00349-9"},{"key":"bibr18-IMP3253","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29139"},{"key":"bibr19-IMP3253","volume-title":"Package insert","author":"ZEPATIER (elbasvir and grazoprevir) tablets, for oral use.","year":"2018"},{"key":"bibr20-IMP3253","volume-title":"Summary of product characteristics","author":"Zepatier (elbasvir 50 mg\/grazoprevir 100 mg) film-coated tablets"},{"key":"bibr21-IMP3253","unstructured":"Health Canada. 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