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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\u003EThis article discusses a study was to evaluating the efficacy of ledipasvir\/sofosbuvir fixed-dose combination in treatment-experienced patients with hepatitis C virus genotype 1 who failed to achieve SVR at week 12 with prior sofosbuvir-based therapy.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections Hepatology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ESofosbuvir plus pegylated interferon \u03b1 (PEG-IFN\u03b1) and ribavirin for 12 weeks or sofosbuvir plus ribavirin for 24 weeks in PEG-IFN\u03b1-ineligible patients is approved for the treatment of patients with hepatitis C virus (HCV) genotype 1 (GT-1) infection. Patients who fail to achieve sustained viral response (SVR) with sofosbuvir-based therapies need effective treatment options. The objective of this study, presented by David L. Wyles, MD, University of California, San Diego, California, USA, was to evaluate the efficacy of ledipasvir\/ sofosbuvir fixed-dose combination (FDC) in treatment-experienced patients with HCV GT-1 who failed to achieve SVR at week 12 (SVR12) with prior sofosbuvir-based therapy.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ELedipasvir is an HCV nonstructural 5A (NS5A) protein inhibitor, sofosbuvir is an HCV nonstructural 5B (NS5B) nucleotide polymerase inhibitor, and ledipasvir\/sofosbuvir FDC is a once-daily, oral FDC (ledipasvir 90 mg\/ sofosbuvir 400 mg) tablet.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EA total of 51 patients who failed to achieve SVR12 in a previous sofosbuvir phase 2\/phase 3 study were retreated with ledipasvir\/sofosbuvir plus weight-based ribavirin. The primary end point was SVR12, defined as HCV RNA below the lower limit of quantification (LLOQ) at post-treatment week 12. The safety end points were adverse event (AE), discontinuation, and laboratory abnormality rates.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe mean patient age was 54 years and 61% of patients were men. The mean baseline HCV RNA log\u003Csub\u003E10\u003C\/sub\u003E was 6.2 IU\/ mL. Prior treatments included sofosbuvir plus PEG-IFN\u03b1\/ ribavirin (n = 25), sofosbuvir with or without ribavirin (n = 21), and sofosbuvir-placebo plus PEG-IFN\u03b1\/ribavirin (n = 5). Most patients were \u003Cem\u003EIL28B\u003C\/em\u003E non-CC (92%) and GT-1a (59%).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EHCV RNA below the LLOQ was achieved by 24% of patients at week 1, 98% at week 4, and 100% of patients at week 8 and at the end of treatment (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Fifty patients (98%) achieved SVR4, SVR12, and SVR24.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022On-Treatment Viral Kinetics and Sustained Viral Response Rates\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2006037694\u0022 data-figure-caption=\u0022On-Treatment Viral Kinetics and Sustained Viral Response Rates\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15574\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EOn-Treatment Viral Kinetics and Sustained Viral Response Rates\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EError bars represent 95% confidence intervals.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EHCV, hepatitis C virus; EOT, end of treatment; LLOQ, lower limit of quantification; SVR, sustained viral response.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from DL Wyles, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EThe 1 patient who relapsed was incorrectly genotyped as GT-1 by line-probe assay at baseline (and in their prior treatment study). Viral sequencing subsequently determined that the patient was GT-3a at baseline and at the time of relapse. The patient had begun retreatment before the viral sequencing results were available.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EResistance analysis showed that no patients had the sofosbuvir-associated variant S282T at baseline. Two patients had the NS5B treatment-emergent variant L159F at baseline and achieved SVR with retreatment. Six patients (12%) had NS5A resistance-associated variants at baseline and achieved SVR with retreatment (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Results of Baseline Resistance Analysis\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2006037694\u0022 data-figure-caption=\u0022Results of Baseline Resistance Analysis\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/48\/22\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15575\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EResults of Baseline Resistance Analysis\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003ENS5A, nonstructural 5A; RAV, resistance associated variant; SVR, sustained viral response.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-5\u0022\u003E\n            \u003Csup\u003Ea\u003C\/sup\u003EOne patient\u0027s baseline results were not available.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-6\u0022\u003EReproduced with permission from DL Wyles, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EAEs were reported in 41 patients (80%), grade 3\/grade 4 AEs were reported in 3 patients (6%), and serious AEs were reported in 2 patients (4%). One patient (2%) discontinued treatment due to AEs. Grade 3\/grade 4 laboratory abnormalities occurred in 9 patients (18%). AEs occurring in \u2265 10% of patients were fatigue (26%), headache (22%), diarrhea (14%), rash (12%), insomnia (10%), and nausea (10%). Most AEs were mild or moderate in severity.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EAmong patients retreated with ledipasvir\/sofosbuvir plus ribavirin for 12 weeks, 98% achieved SVR12. The 1 patient who relapsed had a GT-3a infection. Among patients with HCV GT-1 infection, 100% achieved SVR12. Ledipasvir\/sofosbuvir plus ribavirin treatment for 12 weeks was safe and well tolerated. These data support this treatment regimen as an option for patients with HCV GT-1 infection who have failed to achieve SVR with prior sofosbuvir plus PEG-IFN\u03b1\/ribavirin or sofosbuvir plus ribavirin regimens.\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\/22.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_figures.js?nzofs2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzofs2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}