Open Access Highly Accessed Research

Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients

Stefania Paolucci1, Loretta Fiorina1, Bianca Mariani1, Roberto Gulminetti2, Stefano Novati2, Giorgio Barbarini3, Raffaele Bruno3 and Fausto Baldanti1*

Author Affiliations

1 Molecular Virology Unit, Virology and Microbiology 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

For all author emails, please log on.

Virology Journal 2013, 10:355  doi:10.1186/1743-422X-10-355

Published: 17 December 2013

Abstract

Background

Direct-acting antiviral (DAA) agents target HCV proteins; some of these have already been approved for the treatment of HCV infection, while others are in development. However, selection of DAA-resistant viral variants may hamper treatment. The aim of this study was to illustrate potential natural DAA-resistance mutations in the HCV NS5A and NS5B regions of HCV genotypes 1a and 1b from DAA-naïve patients.

Methods

Direct sequencing of HCV NS5A and NS5B regions was performed in 32 patients infected with HCV genotype 1a and 30 patients infected with HCV genotype 1b; all subjects were naïve to DAAs.

Results

In genotype 1a strains, resistance mutations in NS5A (M28V, L31M and H58P) were observed in 4/32 (12.5%) patients, and resistance mutations in NS5B (V321I, M426L, Y448H, Y452H) were observed in 4/32 (12.5%) patients. In genotype 1b, resistance mutations in NS5A (L28V, L31M, Q54H, Y93H and I280V) were observed in 16/30 (53.3%) patients, while resistance mutations in NS5B (L159F, V321I, C316N, M426L, Y452H, R465G and V499A) were observed in 27/30 (90%) patients.

Conclusions

Mutations conferring DAA resistance were detected in NS5A and NS5B of HCV genotypes 1a and 1b from DAA-naïve patients. Although some mutations confer only a low level of resistance, the presence at baseline of mutated HCV variants should be taken into consideration in the context of DAA therapy.

Keywords:
Hepatitis C virus; HCV baseline resistance; NS5A and NS5B genes; DAA inhibitors