Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial

Hepatology. 2017 Feb;65(2):439-450. doi: 10.1002/hep.28877. Epub 2016 Dec 19.

Abstract

Direct-acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C-SWIFT study was to identify the minimum effective treatment duration across multiple genotypes. C-SWIFT was an open-label, single-center trial in treatment-naïve patients with chronic HCV genotype (GT)1 or 3 infection. All patients received elbasvir (EBR) 50 mg/grazoprevir (GZR) 100 mg with sofosbuvir (SOF) 400 mg for 4-12 weeks. Patients with GT1 infection who failed therapy were eligible for retreatment with EBR/GZR+SOF and ribavirin for 12 weeks. The primary efficacy endpoint was sustained virological response [SVR]12 (SVR of HCV RNA <15 IU/mL 12 weeks after the end of therapy). Rates of SVR12 were 32% (10 of 31) and 87% (26 of 30) in patients without cirrhosis with GT1 infection treated for 4 and 6 weeks and 80% (16 of 20) and 81% (17 of 21) in GT1-infected patients with cirrhosis treated for 6 and 8 weeks. Among GT3-infected patients without cirrhosis, SVR12 was 93% (14 of 15) and 100% (14 of 14) after 8 and 12 weeks. SVR12 in GT3-infected patients with cirrhosis was 83% (10 of 12) after 12 weeks of treatment. Twenty-three GT1-infected patients who relapsed following initial treatment completed retreatment; all achieved SVR12. In the initial treatment phase, there was one serious adverse event of pneumonia, which led to treatment discontinuation, and during retreatment, 1 patient discontinued ribavirin because of pruritus.

Conclusion: Data from this study support the use of 8-week treatment regimens that maintain high efficacy, even for patients with HCV GT3 infection. Retreatment of patients who failed short-duration therapy was achieved through extended treatment duration and addition of ribavirin. (Hepatology 2017;65:439-450).

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amides
  • Benzofurans / administration & dosage*
  • Carbamates
  • Confidence Intervals
  • Cyclopropanes
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Imidazoles / administration & dosage*
  • Male
  • Middle Aged
  • Prospective Studies
  • Quinoxalines / administration & dosage*
  • RNA, Viral / analysis
  • Sulfonamides
  • Time Factors
  • Treatment Outcome
  • Viral Load / drug effects*

Substances

  • Amides
  • Benzofurans
  • Carbamates
  • Cyclopropanes
  • Imidazoles
  • Quinoxalines
  • RNA, Viral
  • Sulfonamides
  • grazoprevir
  • elbasvir