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Virol J. 2012 Oct 24;9:245. doi: 10.1186/1743-422X-9-245.

Naturally occurring mutations to HCV protease inhibitors in treatment-naïve patients.

Author information

  • 1Molecular Virology Unit, Virology and Microbiology Department, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy.

Abstract

BACKGROUND:

Protease inhibitors (PIs) to treat hepatitis C (HCV) virus infection have been approved and others are under development.

RESULTS:

The aims of this study were to illustrate natural polymorphisms in the HCV protease and measure the frequency of PI resistance mutations in different HCV genotypes from PI-naïve patients.Direct sequencing of HCV NS3/4A protease was performed in 156 HCV patients naïve to PIs who were infected with genotype 1a (n = 31), 1b (n = 39), 2 (n = 30), 3 (n = 33) and 4 (n = 23).Amino acid (aa) substitutions associated with HCV PI resistance were found in 17/156 (10.8%) sequences. Mutations V36L, T54S, V55A/I, and Q80K/L were observed in 29% of patients with genotype 1a, and V55F, Q80L/N and M175L in 10% of patients with genotype 1b. The mutation V158M was found in 3% of patients with genotype 2, D168Q was present in 100% of patients with genotype 3 and D168E was observed in 13% of patients with genotype 4. In addition, multiple aa polymorphisms not associated with PI resistance were detected in patients with genotypes 1a, 1b and 4.

CONCLUSIONS:

Although major PI resistance mutations were not detected, other resistance mutations conferring low level resistance to PIs together with a number of natural polymorphisms were observed in proteases of PI naïve HCV patients. A more extensive analysis is needed to better evaluate the impact of baseline resistance and compensatory mutations in the efficacy of HCV PI treatment.

PMID:
23095680
[PubMed - indexed for MEDLINE]
PMCID:
PMC3493344
Free PMC Article

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