Natural NS5A inhibitor resistance associated substitutions in hepatitis C virus genotype 1 infected patients from Italy

Clin Microbiol Infect. 2018 Mar;24(3):308.e5-308.e8. doi: 10.1016/j.cmi.2017.08.003. Epub 2017 Aug 12.


Objectives: Genetic variability in NS5A is associated with different levels of resistance to the currently licensed NS5A inhibitors. The aim of this study was to detect NS5A inhibitor resistance associated substitutions (RASs) in hepatitis C virus (HCV) genotype 1 (GT1) patients who are naive to direct-acting HCV antivirals.

Methods: Amplification, Sanger sequencing and phylogenetic analysis of the HCV NS5A region were performed on plasma obtained from 122 consecutive patients with HCV chronic infection attending four different clinics in Italy.

Results: NS5A inhibitor RASs were detected in 14/61 (23.0%) HCV GT1b and 3/61 (4.9%) HCV GT1a infected patients (p 0.007). The pan-genotypic RAS Y93H was detected in 1 (1.6%) GT1a and 4 (6.6%) GT1b patients. GT1a sequences clustered into two different clades with RASs detected in 1/34 (2.9%) clade I and 2/27 (7.4%) clade II sequences.

Conclusions: Although the impact of naturally occurring NS5A RASs might be limited with upcoming pan-genotypic treatment regimens, this information is still useful to map naturally occurring HCV variants in different geographic areas in the context of current HCV therapy.

Keywords: Direct-acting antivirals; Drug resistance; Hepatitis C virus; NS5A; Pegylated interferon-α and ribavirin.

MeSH terms

  • Drug Resistance, Viral*
  • Female
  • Gene Frequency
  • Genotype*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Phylogeny
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Viral Nonstructural Proteins / genetics*


  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins