Naturally occurring mutations to HCV protease inhibitors in treatment-nave patients

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-nave patients.Direct sequencing of HCV NS3/4A protease was performed in 156 HCV patients nave 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 nave 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. © 2012 Paolucci et al.; licensee BioMed Central Ltd.