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

Stefania Paolucci, Loretta Fiorina, Bianca Mariani, Roberto Gulminetti, Stefano Novati, Giorgio Barbarini, Raffaele Bruno, Fausto Baldanti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number355
JournalVirology Journal
Volume10
DOIs
Publication statusPublished - Dec 17 2013

Keywords

  • DAA inhibitors
  • HCV baseline resistance
  • Hepatitis C virus
  • NS5A and NS5B genes

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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