Randomized study of danoprevir/ritonavir-based therapy for HCV genotype 1 patients with prior partial or null responses to peginterferon/ribavirin

J Hepatol. 2015 Feb;62(2):294-302. doi: 10.1016/j.jhep.2014.09.013. Epub 2014 Sep 18.


Background & aims: Chronic hepatitis C treatment for prior non-responders to peginterferon (PegIFN)/ribavirin remains suboptimal. The MATTERHORN study evaluated regimens containing ritonavir-boosted danoprevir (danoprevir/r) in prior PegIFN alfa/ribavirin non-responders.

Methods: Prior partial responders (N=152) were randomized to 24 weeks of twice-daily danoprevir/r 100/100mg, mericitabine 1000 mg and ribavirin 1000/1200 mg (IFN-free); danoprevir/r plus PegIFN alfa-2a/ribavirin (triple); or danoprevir/r, mericitabine and PegIFN alfa-2a/ribavirin (Quad). Prior null responders (N=229) were randomized to 24 weeks of IFN-free therapy, or quad alone (Quad 24) or quad plus 24-weeks of PegIFN alfa-2a/ribavirin (Quad 48). The primary endpoint was sustained virological response (HCV RNA <25 IU/ml) 24 weeks after end-of-treatment (SVR24). Due to high relapse rates, genotype (G) 1a patients in IFN-free arms were offered additional PegIFN alfa-2a/ribavirin.

Results: Among prior partial responders, SVR24 rates were 46.2%, 51.0%, and 86.0%, in the IFN-free, Triple and Quad arms, respectively; among prior null responders, SVR24 rates were 45.5%, 80.5%, and 83.8% respectively. Relapse rates were lower and SVR24 rates higher in G1b-infected than G1a-infected patients. SVR24 rates in G1a and G1b patients randomized to Quad were 75.0% and 96.2%, respectively, in the partial Quad arm, and 68.1% and 100%, respectively, in the null Quad 24 arm. Treatment failure was associated with resistance to danoprevir, but not to mericitabine, and was more common in G1a infected patients. Treatment was well-tolerated.

Conclusions: Danoprevir/r, mericitabine plus PegIFN alfa-2a/ribavirin was well-tolerated and produced high overall SVR24 rates in prior partial and null responders to PegIFN alfa/ribavirin. In contrast, IFN-free regimens were associated with unacceptably high relapse rates.

Keywords: Danoprevir; Genotype 1; HCV; Mericitabine; Non-responders; Peginterferon/ribavirin; Quad therapy.

Publication types

  • Multicenter Study
  • Observational Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochrome P-450 CYP3A Inhibitors / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Carriers
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Lactams / administration & dosage*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • RNA, Viral / genetics*
  • Recombinant Proteins / administration & dosage
  • Retrospective Studies
  • Ribavirin / administration & dosage*
  • Ritonavir / administration & dosage*
  • Sulfonamides / administration & dosage*
  • Treatment Outcome


  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Carriers
  • Interferon-alpha
  • Lactams
  • RNA, Viral
  • Recombinant Proteins
  • Sulfonamides
  • Polyethylene Glycols
  • Ribavirin
  • danoprevir
  • Ritonavir
  • peginterferon alfa-2a