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J Clin Virol. 2012 Aug;54(4):352-4. doi: 10.1016/j.jcv.2012.04.024. Epub 2012 Jun 1.

Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b.

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  • 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan. fumitakas@toranomon.gr.jp

Abstract

BACKGROUND:

Hepatitis C virus (HCV) of genotype 1b is the most prevalent worldwide, and the least responsive to interferon-based treatments. A combination therapy with two direct-acting antivirals has shown promising results in patients with HCV-1b, but the prevalence of drug-resistant variants before treatment is not known in the Japanese population.

OBJECTIVES:

To detect HCV variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients infected with HCV-1b.

STUDY DESIGN:

Drug-resistant mutations were determined in the 362 hepatitis patients infected with HCV-1b who had not received direct-acting antivirals before.

RESULTS:

Amino-acid substitutions resistant to NS3 inhibitors (V36A, T54S, Q80H and D168E) were detected in 15 of the 307 (4.9%) patients, who had been examined, and T54S (3.3%) predominated over V36A (0.3%), Q80R (0.7%) and D168E (0.7%) in them. Amino-acid substitutions resistant to BMS-790052 (L31M and/or Y93H) were detected in 33 of the 294 (11.2%) patients, and Y93H (8.2%) predominated over L31M (2.7%). One of the 239 (0.4%) patients, who had been examined for amino-acid substitutions in both NS3 and NS5A regions, possessed HCV-1b variants resistant to NS3 inhibitors (T54S) and BMS-790052 (L31M).

CONCLUSIONS:

Mutations conferring resistance to NS3 inhibitors or BMS-790052 were frequent in our treatment-naive study population, but double mutants with possible resistance to both drugs were rare. Since single mutations did not result in treatment failure in a previous pilot trial combining BMS-790052 and an NS3 inhibitor, larger trials of this drug regimen appear warranted in the Japanese population.

PMID:
22658798
DOI:
10.1016/j.jcv.2012.04.024
[PubMed - indexed for MEDLINE]

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