title: Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial.
abstract: OBJECTIVE
  The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations.
  
  
  OBJECTIVE
  To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics.
  
  
  METHODS
  Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012).
  
  
  METHODS
  In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks.
  
  
  METHODS
  The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]).
  
  
  RESULTS
  In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events.
  
  
  CONCLUSIONS
  In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR24 rates of 68% and 48%, respectively.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01441180.
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Anuoluwapo
authors: A
authors: Osinusi
authors: Eric G
authors: EG
authors: Meissner
authors: Yu-Jin
authors: YJ
authors: Lee
authors: Dimitra
authors: D
authors: Bon
authors: Laura
authors: L
authors: Heytens
authors: Amy
authors: A
authors: Nelson
authors: Michael
authors: M
authors: Sneller
authors: Anita
authors: A
authors: Kohli
authors: Lisa
authors: L
authors: Barrett
authors: Michael
authors: M
authors: Proschan
authors: Eva
authors: E
authors: Herrmann
authors: Bhavana
authors: B
authors: Shivakumar
authors: Wenjuan
authors: W
authors: Gu
authors: Richard
authors: R
authors: Kwan
authors: Geb
authors: G
authors: Teferi
authors: Rohit
authors: R
authors: Talwani
authors: Rachel
authors: R
authors: Silk
authors: Colleen
authors: C
authors: Kotb
authors: Susan
authors: S
authors: Wroblewski
authors: Dawn
authors: D
authors: Fishbein
authors: Robin
authors: R
authors: Dewar
authors: Helene
authors: H
authors: Highbarger
authors: Xiao
authors: X
authors: Zhang
authors: David
authors: D
authors: Kleiner
authors: Brad J
authors: BJ
authors: Wood
authors: Jose
authors: J
authors: Chavez
authors: William T
authors: WT
authors: Symonds
authors: Mani
authors: M
authors: Subramanian
authors: John
authors: J
authors: McHutchison
authors: Michael A
authors: MA
authors: Polis
authors: Anthony S
authors: AS
authors: Fauci
authors: Henry
authors: H
authors: Masur
authors: Shyamasundaran
authors: S
authors: Kottilil
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001835:Body Weight; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; D000069474:Sofosbuvir; D014542:Uridine Monophosphate; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
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