title: Four-Week Direct-Acting Antiviral Regimens in Noncirrhotic Patients With Hepatitis C Virus Genotype 1 Infection: An Open-Label, Nonrandomized Trial.
abstract: BACKGROUND
  Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) for 6 weeks achieves sustained virologic response (SVR) rates of 95% in some patients. If effective, shorter therapeutic courses could improve adherence and treatment costs.
  
  
  OBJECTIVE
  To determine factors predictive of SVR to 4 weeks of DAA treatment in patients with stage F0 to F2 liver fibrosis.
  
  
  METHODS
  Open-label, nonrandomized, phase 2a trial. (Clinical Trials.gov: NCT01805882).
  
  
  METHODS
  Single-center.
  
  
  METHODS
  50 treatment-naive and predominantly African American patients with HCV genotype 1 infection and early-stage liver fibrosis were sequentially enrolled into 2 treatment groups.
  
  
  METHODS
  25 participants received a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks, and 25 received a 4-drug regimen consisting of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks.
  
  
  METHODS
  The primary efficacy end point was SVR12 (HCV RNA level below the lower limit of quantification at posttreatment week 12).
  
  
  RESULTS
  Forty percent (10 of 25) (95% CI, 21% to 61%) of patients in the 3-drug group and 20% (5 of 25) (CI, 7% to 41%) of those in the 4-drug group achieved SVR12. Exploratory analysis suggested that lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12. Ten patients had baseline HCV variants conferring greater than 20-fold resistance in vitro to at least 1 study DAA; all had viral relapse. Forty-eight percent (12 of 25) of patients receiving the 3-drug regimen and 72% (18 of 25) of those receiving the 4-drug regimen had adverse events, most of which were mild. One participant was lost to follow-up.
  
  
  CONCLUSIONS
  Nonrandomized study design and small sample of patients with early-stage fibrosis.
  
  
  CONCLUSIONS
  Combination DAA therapy with 3 or 4 drugs for 4 weeks was well-tolerated but resulted in limited cure rates.
  
  
  BACKGROUND
  National Institute of Allergy and Infectious Diseases, National Cancer Institute, and Clinical Center Intramural Program; supported in part by a cooperative research and development agreement between the National Institutes of Health and Gilead Sciences.
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
authors.forename: Sarah
authors.initials: S
authors.lastname: Kattakuzhy
authors.forename: Sreetha
authors.initials: S
authors.lastname: Sidharthan
authors.forename: Amy
authors.initials: A
authors.lastname: Nelson
authors.forename: Mary
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Cassie
authors.initials: C
authors.lastname: Seamon
authors.forename: Eleanor
authors.initials: E
authors.lastname: Wilson
authors.forename: Eric G
authors.initials: EG
authors.lastname: Meissner
authors.forename: Zayani
authors.initials: Z
authors.lastname: Sims
authors.forename: Rachel
authors.initials: R
authors.lastname: Silk
authors.forename: Chloe
authors.initials: C
authors.lastname: Gross
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Akoth
authors.forename: Lydia
authors.initials: L
authors.lastname: Tang
authors.forename: Angie
authors.initials: A
authors.lastname: Price
authors.forename: Tim A
authors.initials: TA
authors.lastname: Jolley
authors.forename: Benjamin
authors.initials: B
authors.lastname: Emmanuel
authors.forename: Michael
authors.initials: M
authors.lastname: Proschan
authors.forename: Gebeyehu
authors.initials: G
authors.lastname: Teferi
authors.forename: Jose
authors.initials: J
authors.lastname: Chavez
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbott
authors.forename: Anuoluwapo
authors.initials: A
authors.lastname: Osinusi
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Polis
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D005663:Furans; C573362:GS-9451; C582393:GS-9669; D011804:Quinolines; D012367:RNA, Viral; D013876:Thiophenes; C586541:ledipasvir; D000069474:Sofosbuvir