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

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

Author information

1
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
2
Hepatology Unit, Policlinic Foundation of Rome Tor Vergata, Rome, Italy.
3
Infectious Diseases, 'Amedeo di Savoia' Hospital, Turin, Italy.
4
1(st) Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy.
5
Molecular Virology, Policlinic Foundation San Matteo, Pavia, Italy.
6
Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Italy.
7
Gastroenterology, 'Cattolica' University of Rome, Rome, Italy.
8
Infectious Diseases, Sant'Andrea Hospital - 'Sapienza' University, Rome, Italy.
9
Gastroepatology, Department of Medical Sciences, City of Health and Science of Turin, University of Turin, Turin, Italy.
10
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. Electronic address: ceccherini@med.uniroma2.it.
11
Clinical Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco, Milan, Italy.
12
Tropical Diseases, Umberto I Hospital -"Sapienza" University, Rome, Italy.
13
Infectious Diseases, Policlinic Foundation of Rome Tor Vergata, Rome, Italy.
14
Infectious Diseases, Sant'Andrea Hospital -"Sapienza" University, Rome, Italy.
15
Infectious Diseases, Ospedale di circolo di Busto Arsizio, ASST valleolona, Varese, Italy.
16
Infectious Diseases, Department of Health Sciences (DISSAL), University of Genoa-AOU IRCCS San Martino-IST, Genova, Italy.
17
Division of Hepatology, University of Genoa-AOU IRCCS San Martino-IST, Genova, Italy.
18
Infectious Diseases, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
19
Infectious Diseases, Hospital Niguarda Ca'Granda, Milan, Italy.
20
Department of Biomedical, Metabolic and Neural Sciences, NOCSAE Baggiovara, Modena, Italy.
21
Gastroenterology, San Camillo Forlanini Hospital, Rome, Italy.
22
Infectious Diseases, "Amedeo di Savoia" Hospital, Turin, Italy.
23
Department of Infectious Diseases, Policlinic Foundation San Matteo, Pavia, Italy.

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.

KEYWORDS:

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

PMID:
28412381
DOI:
10.1016/j.cmi.2017.04.005
[Indexed for MEDLINE]
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