Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life

Clin Microbiol Infect. 2017 Oct;23(10):777.e1-777.e4. doi: 10.1016/j.cmi.2017.04.005. Epub 2017 Apr 12.


Objectives: First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice.

Methods: In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing.

Results: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following three different strategies: A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT-guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided' regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT.

Conclusion: Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.

Keywords: Cirrhosis; Direct acting antivirals; Genotypic resistance testing; HCV failure; HCV resistance; NS5A-inhibitors; Protease-inhibitors; Retreatment.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Female
  • Genotyping Techniques
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Protease Inhibitors / therapeutic use*
  • Retreatment
  • Sequence Analysis, DNA
  • Sustained Virologic Response
  • Treatment Failure


  • Antiviral Agents
  • Protease Inhibitors