Transmission of NS5A-Inhibitor Resistance-Associated Substitutions Among Men Who Have Sex With Men Recently Infected

Stephanie Popping1, Rosanne Verwijs2, Lize Cuypers3,4

  • 1Department of Viroscience, Erasmus Medical Center  , University Medical Center, Rotterdam, The Netherlands.

Insights

Direct-acting antiviral resistance-associated substitutions (RAS) can hinder hepatitis C virus (HCV) cures. A study found that 96% of a large HCV genotype 1a cluster in men who have sex with men harbored the NS5A M28V RAS.

Area of Science:

  • Virology
  • Infectious Diseases
  • Public Health

Background:

  • Direct-acting antiviral (DAA) resistance-associated substitutions (RAS) pose a significant threat to achieving hepatitis C virus (HCV) cure.
  • HCV elimination strategies are challenged by the potential for transmission of drug-resistant viral strains.

Purpose of the Study:

  • To investigate the prevalence and phylogenetic characteristics of HCV genotype 1a infections among recently infected men who have sex with men (MSM).
  • To identify the presence and transmission patterns of resistance-associated substitutions (RAS) within this population.

Main Methods:

  • Phylogenetic analysis was employed to examine the genetic relatedness of HCV genotype 1a strains.
  • Viral sequences from 87 recently infected MSM were analyzed to identify specific RAS, including NS5A M28V.

Main Results:

  • A substantial proportion of participants (28/87, approximately 32%) belonged to a large, distinct phylogenetic cluster.
  • Within this cluster, a high prevalence of the NS5A M28V RAS was observed, with 96% of individuals harboring this substitution.

Conclusions:

  • The findings highlight the potential for rapid transmission of HCV genotype 1a with specific DAA RAS within the MSM population.
  • The high prevalence of the NS5A M28V RAS in a major cluster underscores a significant challenge for HCV treatment and elimination efforts.