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

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

Stefania Paolucci, Loretta Fiorina, Antonio Piralla, Roberto Gulminetti, Stefano Novati, Giorgio Barbarini, Paolo Sacchi, Marta Gatti, Luca Dossena and Fausto Baldanti

Virology Journal 2012, 9:245 doi:10.1186/1743-422X-9-245
Published: 24 October 2012

The complete article is available as a provisional PDF

Abstract (provisional)
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-naive patients.

Direct sequencing of HCV NS3/4A protease was performed in 156 HCV patients naive 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 naive 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.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

http://www.virologyj.com/content/9/1/245/abstract