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J Clin Virol. 2015 Nov;72:114-8. doi: 10.1016/j.jcv.2015.08.015. Epub 2015 Sep 12.

Development and persistence of DAA resistance associated mutations in patients failing HCV treatment.

Author information

1
Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.
2
Institute of Infectious Diseases, University of Pavia, 27100, Pavia, Italy.
3
Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.
4
Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100, Pavia, Italy. Electronic address: f.baldanti@smatteo.pv.it.

Abstract

BACKGROUND:

Direct-acting antiviral agents (DAAs) combined with pegylated-interferon (PegIFN) and ribavirin (RBV) are still a standard treatment in patients with genotype 1HCV infection. However, virologic response could be impaired by baseline or early selection of resistant HCV strains.

OBJECTIVES:

The aim of this study was to determine the onset and persistence of resistance-associated mutations (RAMs) in the NS3 and NS5B genes of DAA-naïve patients failing treatment.

STUDY DESIGN:

Direct sequencing of HCV NS3 was performed in 49 DAA-naïve patients with HCV genotype 1 infection.

RESULTS:

Eight out of 23 patients (34.7%) failed PegIFN/RBV/telaprevir during the 12-weeks of therapy. Treatment failure was associated with the development of RAMs at amino-acids 36,54,80 and 155 of the HCV protease in 6/8 patients (75%). Among patients treated with PegIFN/RBV/boceprevir treatment, 4/18 (22.2%) failed therapy. Of these, 2 (50%) carried virus strains which developed a RAM at amino-acids 54 and 155. Among HCV strains with RAMs, 7 belonged to genotype 1a and 1 to 1b. Finally, in 6/10 (60%) patients, drug-resistant variants could still be detected for up to 3-7 months after stopping therapy.

CONCLUSIONS:

A higher rate (p=0.49) of treatment failure was observed in patients receiving telaprevir- compared to the boceprevir-based combination. In addition, compared with genotype 1b, genotype 1a was associated with higher rates (p=0.01) of treatment failure due to virus resistant strains. Resistance testing at baseline and during DAA treatment should be taken into consideration when treating patients with new HCV combination therapies.

KEYWORDS:

Drug resistance; HCV genotype 1; Hepatitis C virus; Protease inhibitors; Sequencing

PMID:
26489401
DOI:
10.1016/j.jcv.2015.08.015
[Indexed for MEDLINE]

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