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. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

Cento, V;
2017

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. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Cirrhosis
Direct acting antivirals
Genotypic resistance testing
HCV failure
HCV resistance
NS5A-inhibitors
Protease-inhibitors
Retreatment
Adult
Aged
Antiviral Agents
Female
Genotyping Techniques
Hepacivirus
Hepatitis C, Chronic
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Protease Inhibitors
Retreatment
Sequence Analysis, DNA
Sustained Virologic Response
Treatment Failure
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11699/65783
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