{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:02:44Z","timestamp":1792587764388,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"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":[[2018,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Daclatasvir (DCV; non-structural [NS]5A inhibitor) plus asunaprevir (ASV; NS3 inhibitor) plus beclabuvir (BCV; non-nucleoside NS5B inhibitor) is an approved regimen for hepatitis C virus (HCV) genotype (GT)-1 treatment in Japan. A comprehensive analysis of pre-treatment and treatment-emergent HCV resistance to this regimen \u00b1 ribavirin (RBV) was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were pooled from five Phase 2\/3 studies of DCV+ASV+BCV\u00b1RBV given for 12 weeks to GT-1a- or GT-1b-infected patients. The prevalence and impact of pre-treatment resistance-associated substitutions (RAS) in NS5A, NS3, and NS5B on sustained virological response (SVR) was assessed, as were emergent RAS and their post-treatment persistence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline NS5A RAS (GT-1a: M28T, Q30H\/L\/R\/S, L31M, Y93C\/H; GT-1b: L31I\/M, Y93C\/H) were present in 5% (26\/561) of GT-1a and 16% (85\/537) of GT-1b sequences. SVR12 for GT-1b without RBV was 100% (82\/82) with RAS and &gt;99% (427\/428) without RAS. For GT-1a, SVR12 without RAS was 97% (85\/88) with RBV and 92% (410\/447) without RBV; SVR12 with RAS was 100% (2\/2) with RBV and 54% (13\/24) without RBV. Baseline NS3 (at R155 or D168) and NS5B (at P495) RAS were rare (\u22641%). Treatment-emergent NS5A RAS (mostly Q30E\/H\/K\/R+Y93H\/N) in GT-1a persisted 60 weeks post-treatment, while NS3 RAS (mostly R155K) and NS5B-P495L\/S were no longer detected after 48 or 24 weeks, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DCV+ASV+BCV+RBV was highly efficacious in HCV GT-1 infection, including HCV GT-1b with NS5A RAS. The fitness of treatment-emergent RAS post-treatment was NS5A &gt; NS3 &gt; NS5B; NS3 and NS5B RAS were generally replaced by wild-type sequence within 48 weeks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3177","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T08:39:15Z","timestamp":1496911155000},"page":"53-66","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Pooled Analysis of HCV Genotype 1 Resistance-Associated Substitutions in NS5A, NS3 and NS5B pre- and Post-Treatment with 12 Weeks of Daclatasvir, Asunaprevir and Beclabuvir"],"prefix":"10.1177","volume":"23","author":[{"given":"Fiona","family":"McPhee","sequence":"first","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ueland","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yu","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Vellucci","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuning","family":"Wang","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Shinjuku, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyasu","family":"Karino","sequence":"additional","affiliation":[{"name":"Sapporo K\u03c9sei General Hospital, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Kumada","sequence":"additional","affiliation":[{"name":"Toranomon Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"bibr1-IMP3177","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26744"},{"key":"bibr2-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.5.3225-3229.1992"},{"key":"bibr3-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/S1089-3261(02)00065-X"},{"key":"bibr4-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.06.014"},{"key":"bibr5-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.01.003"},{"key":"bibr6-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02495-13"},{"key":"bibr7-IMP3177","doi-asserted-by":"publisher","DOI":"10.1126\/science.7824947"},{"key":"bibr8-IMP3177","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104430"},{"key":"bibr9-IMP3177","doi-asserted-by":"publisher","DOI":"10.1038\/nature08960"},{"key":"bibr10-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01186-12"},{"key":"bibr11-IMP3177","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12964"},{"key":"bibr12-IMP3177","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3860"},{"key":"bibr13-IMP3177","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3868"},{"key":"bibr14-IMP3177","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1245-6"},{"key":"bibr15-IMP3177","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13796"},{"key":"bibr16-IMP3177","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw336"},{"key":"bibr17-IMP3177","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv379"},{"key":"bibr18-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2012.12.020"},{"key":"bibr19-IMP3177","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-015-0221-5"},{"key":"bibr20-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00556-10"},{"key":"bibr21-IMP3177","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26388"},{"key":"bibr22-IMP3177","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2729"},{"key":"bibr23-IMP3177","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vew024"},{"key":"bibr24-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00308-12"},{"key":"bibr25-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61059-X"},{"key":"bibr26-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01209-12"},{"key":"bibr27-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.24.13225-13231.2003"},{"key":"bibr28-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03851-14"},{"key":"bibr29-IMP3177","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-016-0354-1"},{"key":"bibr30-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.012"},{"key":"bibr31-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.025"},{"key":"bibr32-IMP3177","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1825"},{"key":"bibr33-IMP3177","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24594"},{"key":"bibr34-IMP3177","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05854-11"},{"key":"bibr35-IMP3177","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3120"},{"key":"bibr36-IMP3177","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25581"},{"issue":"2","key":"bibr37-IMP3177","first-page":"S473","volume":"56","author":"McPhee F.","year":"2012","journal-title":"J Hepatol"},{"key":"bibr38-IMP3177","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6346(00)00074-7"},{"key":"bibr39-IMP3177","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/26.4.404"},{"key":"bibr40-IMP3177","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.581"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3177","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:52:21Z","timestamp":1777380741000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP3177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.3851\/IMP3177"],"URL":"https:\/\/doi.org\/10.3851\/imp3177","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]}}}