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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe prowess of the nucleotide polymerase inhibitor sofosbuvir (SOF) against hepatitis C virus (HCV) is known. This article presents results from a study investigating a 12-week fixed-dose combination of SOF and nonstructural protein 5A (NS5A) inhibitor GS-5816 regimen in noncirrhotic, treatment-na\u00efve HCV genotype 1 patients.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions Viral Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAn oral, once-daily, 12-week, fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir (SOF) and nonstructural protein 5A (NS5A) inhibitor GS-5816 (ledipasvir) yields high rates of sustained virological response 12 weeks after therapy (SVR12) in noncirrhotic patients infected with genotypes 1 to 6 of hepatitis C virus (HCV). The results of the open-label study were presented by Tram Tran, MD, Cedars-Sinai Hospital, Los Angeles, California, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe prowess of SOF against HCV is known [Jacobson IM et al. \u003Cem\u003ENew Engl J Med.\u003C\/em\u003E 2013; Lawitz E et al. \u003Cem\u003ENew Engl J Med.\u003C\/em\u003E 2013]. High SVR following a 12-week GS-5816 regimen in noncirrhotic, treatment-na\u00efve HCV genotype 1 to 6 patients has been described.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn part A of the current study, patients infected with HCV genotype 1 (n = 55), genotype 3 (n = 54), and genotypes 2, 4, 5, and 6 (n = 45) received oral, ribavirin-free, once-daily SOF + GS-5816 25 mg or 100 mg for 12 weeks. SVR12 was consistently high for the 25-mg and 100-mg doses: genotype 1 (26\/27, 96% and 28\/28, 100%), genotype 2 (10\/11, 91% and 10\/10, 100%), genotype 3 (25\/27, 93% and 25\/27, 93%), genotype 4 (7\/7, 100% and 6\/7, 86%), genotype 5 (25 mg only: 1\/1, 100%), and genotype 6 (4\/4, 100% and 5\/5, 100%). The relatively lower SVR12 for the 100-mg genotype 4 patients reflected the loss of 1 patient to follow-up.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EPart B of the study focused on genotype 1 (n = 120) and 2 (n = 103) noncirrhotic, treatment-na\u00efve patients and involved an 8-week treatment with the 25-mg and 100-mg doses of SOF + GS-5816 without or with (1000 to 1200 mg\/d) ribavirin.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe primary objective of part B was the evaluation of safety (adverse events [AEs], laboratory abnormalities) and efficacy. The primary efficacy end point was SVR12, with an HCV RNA lower limit of 25 IU\/mL.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDemographics of the 4 treatment arms were similar. The completion rate was 98% to 100%, with 1 discontinuation because of an AE in the SOF + GS-5816 25 mg arm and 1 case of noncompliance in the SOF + GS-5816 100 mg + ribavirin arm.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ESVR12 in genotype 1 patients receiving the 25-mg dose without and with ribavirin was 87% (26\/30; 3 relapses and 1 AE-related discontinuation) and 83% (25\/30; 5 relapses), respectively. The respective value for the 100-mg dose was 90% (26\/29; 3 relapses) and 81% (25\/31; 5 relapses and 1 lost to follow-up). SVR12 in genotype 2 patients receiving the 25-mg dose without and with ribavirin was 77% (20\/26; 6 relapses) and 88% (22\/25; 2 relapses and 1 lost to follow-up), respectively. The respective value for the 100-mg dose was 88% (23\/26; 3 relapses) and 88% (23\/26; 3 relapses).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EAEs were similar in the 4 arms. The 4 grade 3 to 4 AEs in the SOF + GS-5816 25 mg arm were not treatment related. Relatively frequent AEs mainly comprised fatigue, headache, nausea, and nasopharyngitis. They were manageable.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThe 12-week regimen produced SVR12 rates exceeding 90% in all HCV genotypes. The 8-week regimen was less effective, with lower SVR rates and higher relapse rates in HCV genotype 1 and 2 patients. Inclusion of ribavirin did not affect safety and tolerability. SOF 400 mg and GS-5816 100 mg have been coformulated in a fixed-dose combination for a phase 3 study.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/48\/17.1.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzofi1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}