A. Osinusi|Eric G. Meissner|Yu Jin Lee|Dimitra Bon|Laura Heytens|Amy Nelson|Michael C. Sneller|Anita Kohli|Lisa Barrett|Michael A. Proschan|Eva Herrmann|Bhavana Shivakumar|Wenjuan Gu|Richard Kwan|Geb Teferi|Rohit Talwani|Rachel Silk|Colleen Kotb|Susan Wróblewski|Dawn Fishbein|Robin Dewar|Helene Highbarger|Xiao Zhang|David E. Kleiner|Bradford J. Wood|José Chávez|William T. Symonds|Mani Subramanian|John G. McHutchison|Michael A. Polis|Anthony S. Fauci|Henry Masur|Shyamasundaran Kottilil
Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics
National Institute of Allergy and Infectious Diseases|National Institutes of Health
efficacy directly acting antiviral agents interferonfree regimens treatment chronic hepatitis c infections needs evaluated different populationsto determine efficacy safety sofosbuvir weightbased lowdose ribavirin among population unfavorable treatment characteristicssinglecenter randomized 2part openlabel phase 2 study involving 60 treatmentnaive patients hepatitis c virus hcv genotype 1 enrolled national institutes health october 2011april 2012in studys first part 10 participants early moderate liver fibrosis treated 400 mgd sofosbuvir weightbased ribavirin 24 weeks second part 50 participants stages liver fibrosis randomized 11 receive 400 mg sofosbuvir either weightbased lowdose 600 mgd ribavirin 24 weeksthe primary study end point proportion participants undetectable hcv viral load 24 weeks treatment completion sustained virologic response 24 weeks svr24in first part study 9 participants 90 95 ci 55100 achieved svr24 second part 7 participants 28 weightbased group 10 40 lowdose group relapsed treatment completion leading svr24 rates 68 95 ci 4685 weightbased group 48 95 ci 2869 p 20 lowdose group twenty individuals participated pharmacokineticviral kinetic substudy demonstrated slower loss rate infectious virus relapsers participants achieved svr clearance 357d vs 560d p 009 frequent adverse events headache anemia fatigue nausea 7 grade 3 events including anemia neutropenia nausea hypophosphatemia cholelithiasis pancreatitis one discontinued treatment due adverse eventsin population patients high prevalence unfavorable traditional predictors treatment response 24week regimen sofosbuvir weightbased lowdose ribavirin resulted svr24 rates 68 48 respectivelyclinicaltrialsgov identifier nct01441180