title: Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: a randomized, 28-day, dose-ranging trial.
abstract: OBJECTIVE
  Sofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-naïve patients infected with genotype 1 HCV.
  
  
  METHODS
  In this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400mg) or placebo plus PegIFN/RBV for 28 days, after which all patients continued to receive PegIFN/RBV alone for a further 44 weeks.
  
  
  RESULTS
  Patients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5 log₁₀ IU/ml (-5.3 for 100 mg, -5.1 for 200 mg and -5.3 for 400 mg) vs. -2.8 log₁₀ IU/ml for placebo/PegIFN/RBV after 28 days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94%) than placebo (21%), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56%, 83%, and 80% for sofosbuvir 100, 200, and 400 mg, respectively, vs. 43% for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100 mg group than sofosbuvir 200 and 400 mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea.
  
  
  CONCLUSIONS
  These results support further studies with sofosbuvir at 200 mg and 400 mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.
authors.affiliation: Fundacion de Investigacion, San Juan, Puerto Rico. mrodrigueztorres@fdipr.com
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Edwin
authors.initials: E
authors.lastname: Dejesus
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Melanie T
authors.initials: MT
authors.lastname: Cornpropst
authors.forename: Michael
authors.initials: M
authors.lastname: Mader
authors.forename: Efsevia
authors.initials: E
authors.lastname: Albanis
authors.forename: Deyuan
authors.initials: D
authors.lastname: Jiang
authors.forename: Christy M
authors.initials: CM
authors.lastname: Hebner
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Berrey
authors.forename: Jay
authors.initials: J
authors.lastname: Lalezari
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D000069474:Sofosbuvir; D013997:Time Factors; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014542:Uridine Monophosphate; C100416:peginterferon alfa-2a; D000069474:Sofosbuvir