{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:48:30Z","timestamp":1761562110539},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,5,15]],"date-time":"2016-05-15T00:00:00Z","timestamp":1463270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Summary<\/jats:title>High rates of sustained virologic response (SVR<\/jats:styled-content>) has been achieved in Japanese patients with chronic hepatitis C virus (HCV<\/jats:styled-content>) genotype (GT<\/jats:styled-content>)1 and GT<\/jats:styled-content>2 infection treated with ledipasvir\/sofosbuvir (LDV<\/jats:styled-content>\/SOF<\/jats:styled-content>) \u00b1ribavirin (RBV<\/jats:styled-content>) and SOF<\/jats:styled-content>+RBV<\/jats:styled-content>, respectively. We evaluated the effect of baseline HCV NS<\/jats:styled-content>5A and NS<\/jats:styled-content>5B resistance\u2010associated variants (RAV<\/jats:styled-content>s) on treatment outcome and characterized variants at virologic failure.<\/jats:p>Baseline deep sequencing for NS<\/jats:styled-content>5A and NS<\/jats:styled-content>5B genes was performed for all GT<\/jats:styled-content>1 patients. Deep sequencing of NS<\/jats:styled-content>5A (GT<\/jats:styled-content>1 only) and NS<\/jats:styled-content>5B (GT<\/jats:styled-content>1 and GT<\/jats:styled-content>2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA<\/jats:styled-content> (i.e., >25 IU<\/jats:styled-content>\/mL<\/jats:styled-content>). In patients with HCV GT<\/jats:styled-content>1 infection, 22.3% (GT<\/jats:styled-content>1a: 2\/11; GT<\/jats:styled-content>1b: 74\/330) had \u22651 baseline NS<\/jats:styled-content>5A RAV<\/jats:styled-content>. The most frequent NS<\/jats:styled-content>5A RAV<\/jats:styled-content>s in GT<\/jats:styled-content>1b were Y93H (17.9%, 59\/330) and L31M (2.4%, 8\/330). Despite the presence of NS<\/jats:styled-content>5A RAV<\/jats:styled-content>s at baseline, 100% and 97% of patients achieved SVR<\/jats:styled-content>12, compared with 100% and 99% for those with no NS<\/jats:styled-content>5A RAV<\/jats:styled-content>s with LDV<\/jats:styled-content>\/SOF<\/jats:styled-content> and LDV<\/jats:styled-content>\/SOF<\/jats:styled-content>+RBV<\/jats:styled-content>, respectively. All patients with NS<\/jats:styled-content>5B RAV<\/jats:styled-content>s at baseline achieved SVR<\/jats:styled-content>12. Of the 153 patients with GT<\/jats:styled-content>2 infection (GT<\/jats:styled-content>2a 60.1%, GT<\/jats:styled-content>2b 39.9%), 3.3% (5\/153) experienced viral relapse. No S282T or other NS<\/jats:styled-content>5B RAV<\/jats:styled-content>s were detected at baseline or relapse; no change in susceptibility to SOF<\/jats:styled-content> or RBV<\/jats:styled-content> was observed at relapse. In conclusion, LDV<\/jats:styled-content>\/SOF<\/jats:styled-content> and SOF<\/jats:styled-content>+RBV<\/jats:styled-content> demonstrate a high barrier to resistance in Japanese patients with HCV GT<\/jats:styled-content>1 and GT<\/jats:styled-content>2 infection. The presence of baseline NS<\/jats:styled-content>5A RAV<\/jats:styled-content>s did not impact treatment outcome in GT<\/jats:styled-content>1 Japanese patients treated with LDV<\/jats:styled-content>\/SOF<\/jats:styled-content> for 12 weeks.<\/jats:p>","DOI":"10.1111\/jvh.12549","type":"journal-article","created":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T03:11:27Z","timestamp":1463713887000},"page":"780-788","source":"Crossref","is-referenced-by-count":34,"title":["Resistance Analyses of Japanese Hepatitis C\u2010Infected Patients Receiving Sofosbuvir or Ledipasvir\/Sofosbuvir Containing Regimens in Phase 3 Studies"],"prefix":"10.1111","volume":"23","author":[{"given":"M.","family":"Mizokami","sequence":"first","affiliation":[{"name":"The Research Center for Hepatitis & Immunology National Center for Global Health and Medicine Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Dvory\u2010Sobol","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Izumi","sequence":"additional","affiliation":[{"name":"Musashino Red Cross Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Nishiguchi","sequence":"additional","affiliation":[{"name":"Hyogo College of Medicine Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Doehle","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. S.","family":"Svarovskaia","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"De\u2010Oertel","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Knox","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. M.","family":"Brainard","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Mo","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Hokkaido University Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Takehara","sequence":"additional","affiliation":[{"name":"Osaka University Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Omata","sequence":"additional","affiliation":[{"name":"Yamanashi Prefectural Hospital Organization Yamanashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,5,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000252782"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12272"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12020"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30531"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23691"},{"key":"e_1_2_10_7_1","volume-title":"Guidelines for the Management of Hepatitis C Virus Infection: Edition 3.4 [Japanese]","author":"The Japan Society of Hepatology","year":"2015"},{"key":"e_1_2_10_8_1","volume-title":"The MHLW Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis: 2015 Guidelines for the Management of Hepatitis B\/C Virus Infection [Japanese]","year":"2015"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26388"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27113"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27567"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12312"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214854"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.12.029"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402454"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316366"},{"key":"e_1_2_10_17_1","first-page":"1128A","article-title":"Baseline and Post\u2010baseline Resistance Analyses of Phase 2\/3 Studies of Ledipasvir\/Sofosbuvir \u00b1 RBV","volume":"60","author":"Christoph SH\u2010S","year":"2014","journal-title":"Hepatology"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00054-12"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/095632020601700203"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00433-06"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70033-1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62121-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.03.045"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit562"},{"key":"e_1_2_10_25_1","unstructured":"SnoeckR AndreiG Hol\u00fdA DeCE.Antiherpetic activity of new acyclic nucleoside phosphonate derivatives. 36th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1996 Sep 15\u201018; New Orleans La: Washington DC: American Society for Microbiology; 1996. p. 130."},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu697"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70099-X"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/10665270050081478"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199202133260703"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.012"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv564"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12549","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T06:22:46Z","timestamp":1695536566000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,15]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/jvh.12549"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12549","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,15]]}}}