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.

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. Menzaghi, L.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. - In: CLINICAL MICROBIOLOGY AND INFECTION. - ISSN 1198-743X. - 23:10(2017 Oct), pp. 777.e1-777.e4.

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

Cento, V.;Perno, C. F.;Micheli, V.;Menzaghi, B.;
2017-10

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.
Cirrhosis; Direct acting antivirals; Genotypic resistance testing; HCV failure; HCV resistance; NS5A-inhibitors; Protease-inhibitors; Retreatment; Microbiology (medical); Infectious Diseases
Settore MED/07 - Microbiologia e Microbiologia Clinica
CLINICAL MICROBIOLOGY AND INFECTION
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/623233
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