Baseline and post-treatment hepatitis C NS5A resistance in relapsed patients from a multicentric real-life cohort

Antivir Ther. 2018;23(4):307-314. doi: 10.3851/IMP3184.

Abstract

Background: Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors.

Methods: From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients.

Results: Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance).

Conclusions: This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment.

Publication types

  • Multicenter Study

MeSH terms

  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • DNA Mutational Analysis
  • Drug Resistance, Viral*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy
  • Hepatitis C / virology*
  • Humans
  • Male
  • Treatment Failure
  • Treatment Outcome
  • Viral Load
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / genetics*

Substances

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