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

• Published in: Clinical microbiology and infection Vol. 23; no. 10; pp. 777.e1 - 777.e4
• Main Authors: 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., Menzaghi, B., Nicolini, L.A., Marenco, S., Di Maio, V.C., Aragri, M., Pecchioli, A., Bertoli, A., Sarrecchia, C., Macera, M., Coppola, N., Puoti, M., Romagnoli, D., Pellicelli, A., Bonora, S., Novati, S., Baldanti, F., Ghisetti, V., Andreoni, M., Taliani, G., Rizzardini, G., Angelico, M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2017
• Subjects: Adult; Aged; Antiviral Agents - therapeutic use; Cirrhosis; Direct acting antivirals; Female; Genotypic resistance testing; Genotyping Techniques; HCV failure; HCV resistance; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C, Chronic - drug therapy; Humans; Male; Microbial Sensitivity Tests; Middle Aged; NS5A-inhibitors; Protease Inhibitors - therapeutic use; Protease-inhibitors; Retreatment; Sequence Analysis, DNA; Sustained Virologic Response; Treatment Failure; Cirrhosis; Retreatment; Genotypic resistance testing; HCV resistance; Direct acting antivirals; HCV failure; Protease-inhibitors; NS5A-inhibitors
• ISSN: 1198-743X; 1469-0691
• DOI: 10.1016/j.cmi.2017.04.005

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.
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.
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.
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.