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

V. Cento, S. Barbaliscia, I. Lenci, T. Ruggiero, C. F. Magni, S. Paolucci, S. Babudieri, M. Siciliano, C. Pasquazzi, A. Ciancio, C. F. Perno, F. Ceccherini-Silberstein, V. Micheli, Y. Troshina, E. Biliotti, M. Milana, M. Melis, E. Teti, L. Lambiase, B. MenzaghiL. A. Nicolini, S. Marenco, V. C. Di Maio, M. Aragri, A. Pecchioli, A. Bertoli, C. Sarrecchia, M. Macera, N. Coppola, M. Puoti, D. Romagnoli, A. Pellicelli, S. Bonora, S. Novati, F. Baldanti, V. Ghisetti, M. Andreoni, G. Taliani, G. Rizzardini, M. Angelico, on behalf of, the HCV retreatment team VIRONET-C study group

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)777.e1-777.e4
JournalClinical Microbiology and Infection
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • Cirrhosis
  • Direct acting antivirals
  • Genotypic resistance testing
  • HCV failure
  • HCV resistance
  • NS5A-inhibitors
  • Protease-inhibitors
  • Retreatment

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Cento, V., Barbaliscia, S., Lenci, I., Ruggiero, T., Magni, C. F., Paolucci, S., Babudieri, S., Siciliano, M., Pasquazzi, C., Ciancio, A., Perno, C. F., Ceccherini-Silberstein, F., Micheli, V., Troshina, Y., Biliotti, E., Milana, M., Melis, M., Teti, E., Lambiase, L., ... the HCV retreatment team VIRONET-C study group (2017). Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life. Clinical Microbiology and Infection, 23(10), 777.e1-777.e4. https://doi.org/10.1016/j.cmi.2017.04.005