{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:51:00Z","timestamp":1777452660280,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"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":[[2016,11]]},"abstract":"\n Background<\/jats:title>\n Ledipasvir\/sofosbuvir \u00b1 ribavirin administered for 12 weeks to patients with genotype-1 HCV infection and compensated cirrhosis is effective and well-tolerated. The Phase II TRILOGY-1 and TRILOGY-2 studies investigated whether ledipasvir\/sofosbuvir plus the non-nucleotide NS5B inhibitor GS-9669 or the NS3\/4A protease inhibitor vedroprevir could reduce treatment duration and\/or eliminate the need for ribavirin in genotype-1 HCV-infected patients with compensated cirrhosis.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In TRILOGY-1, 100 cirrhotic patients were randomized (1:1:1) to 8 weeks of ledipasvir\/sofosbuvir plus ribavirin, ledipasvir\/sofosbuvir plus GS-9669 250 mg or ledipasvir\/sofosbuvir plus GS-9669 500 mg. In TRIL-OGY-2, 46 previously treated cirrhotic patients were randomized (1:1) to 8 weeks of ledipasvir\/sofosbuvir plus vedroprevir \u00b1 ribavirin. The primary end points were the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12) and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In both studies, most patients were male (each 65%) and white (92\u201396%), infected with HCV genotype-1a (62\u201370%) and had IL28B non-CC genotypes (82\u201387%). In total, 37\u201339% of patients were Hispanic or Latino. SVR12 rates were similar across treatment arms in TRIL-OGY-1 (82\u201391%) and TRILOGY-2 (88\u201395%); no patient had on-treatment virological failure. Two serious adverse events (acute myocardial infarction and cardiomyopathy) were reported in two patients participating in TRILOGY-1, both of whom had pre-existing cardiac conditions. Laboratory abnormalities were infrequent.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n All ledipasvir\/sofosbuvir-based regimens were well-tolerated. To shorten therapy and eliminate ribavirin, use of a more potent third agent or a third agent with a different mechanism of action may be required.<\/jats:p>\n <\/jats:sec>","DOI":"10.3851\/imp3062","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T11:02:25Z","timestamp":1467025345000},"page":"679-687","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Ledipasvir\/Sofosbuvir-Based Treatment of Patients with Chronic Genotype-1 HCV Infection and Cirrhosis: Results from Two Phase II Studies"],"prefix":"10.1177","volume":"21","author":[{"given":"Eric","family":"Lawitz","sequence":"first","affiliation":[{"name":"Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Poordad","sequence":"additional","affiliation":[{"name":"Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H","family":"Hyland","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadas","family":"Dvory-Sobol","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana M","family":"Brainard","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G","family":"McHutchison","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio A","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,11,1]]},"reference":[{"key":"bibr1-IMP3062","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1302973"},{"key":"bibr2-IMP3062","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2015.07.002"},{"key":"bibr3-IMP3062","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27259"},{"key":"bibr4-IMP3062","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402454"},{"key":"bibr5-IMP3062","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316366"},{"key":"bibr6-IMP3062","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70050-2"},{"key":"bibr7-IMP3062","volume-title":"Prescribing information","author":"HARVONI (ledipasvir and sofosbuvir).","year":"2015"},{"key":"bibr8-IMP3062","unstructured":"AASLD\/IDSA HCV Guidance Panel. Hepatitis C guidance: recommendations for testing, managing, and treating hepatitis C. (Updated March 2016. Accessed 23 March 2016.) Available from http:\/\/www.hcvguidelines.org\/full-report\/initial-treatment-hcv-infection."},{"key":"bibr9-IMP3062","unstructured":"AASLD\/IDSA HCV Guidance Panel. Hepatitis C guidance: recommendations for testing, managing, and treating hepatitis C. (Updated March 2016. Accessed 23 March 2016.) http:\/\/www.hcvguidelines.org\/full-report\/retreatment-persons-whom-prior-therapy-has-failed."},{"key":"bibr10-IMP3062","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.11.007"},{"key":"bibr11-IMP3062","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61228-9"},{"key":"bibr12-IMP3062","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2415"},{"key":"bibr13-IMP3062","volume-title":"Prescribing information","author":"COPEGUS (ribavirin).","year":"2015"},{"key":"bibr14-IMP3062","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/26.4.404"},{"key":"bibr15-IMP3062","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3062","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:52:04Z","timestamp":1777380724000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP3062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,1]]},"references-count":15,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.3851\/IMP3062"],"URL":"https:\/\/doi.org\/10.3851\/imp3062","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,1]]}}}