HCV: triplet salvage therapy yields impressive results

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  • Grazoprevir/uprifosbuvir/ruzasvir, with/without ribavirin (RBV), is highly effective for clearing HCV after failure of NS5A inhibitor-containing all-oral direct-acting antiviral (DAA) regimens.

Why this matters

  • Patients who fail DAAs have limited options.
  • Grazoprevir/uprifosbuvir/ruzasvir combines a NS3 protease inhibitor, nucleotide NS5B polymerase inhibitor, and an NS5A inhibitor.

Study design

  • 2 open-label, international phase 2 studies of patients with relapse after all-oral NS5A inhibitor-containing regimens: C-SURGE (N=93) and C-CREST Part C (N=24).
  • All received salvage therapy with grazoprevir/uprifosbuvir/ruzasvir for 16 wk (with RBV) or 24 wk (RBV-free).
  • Primary endpoint: Sustained virologic response at 12 wk posttherapy (SVR12).
  • Funding: Merck.

Key results

  • Overall SVR12 was 98.3% (115/117).
  • C-SURGE: SVR12 rate in HCV-1 (1a, 86%) was 100% with 24-wk RBV-free regimen (n=49), and 97.7% with 16-wk RBV-included regimen (n=43/44); 1 patient was lost to follow-up.
  • C-CREST: SVR12 rate with 16-wk RBV-included regimen was 100% in HCV-1 (n=2), 92.9% in HCV-2 (n=13/14), and 100% in HCV-3 (n=8); 1 patient stopped treatment after 1 dose because of serious vomiting/tachycardia.
  • Presence of baseline resistance associated substitutions (RAS) had no effect on SVR12; in C-SURGE, 84% had an NS5A RAS and 65% had an NS3 RAS.


  • Small size.
  • No patients in C-CREST part C were cirrhotic (C-SURGE, 42%).