Q80K Polymorphism Screening

The Q80K Polymorphism

Polymorphisms are natural genetic variations that occur in a population at variable frequencies. The Q80K polymorphism in hepatitis C virus (HCV) has been observed in 35% of patients infected with HCV genotype 1 and in greater than 40% of patients with HCV genotype 1a in the United States, where genotype 1a represents approximately 75% of HCV genotype 1 infections overall.1 The Q80K polymorphism has been shown to alter the NS3/4A protease in a way that substantially reduces the efficacy of simeprevir (Olysio®), an FDA-approved protease inhibitor indicated for use with pegylated interferon alpha and ribavirin (peg-IFN/RBV).1

Impact of Q80K Polymorphism Screening

  • Clinical trials have shown that the efficacy of simeprevir in combination with peg-IFN/RBV in genotype 1a-infected patients was substantially reduced when the Q80K polymorphism was detected at baseline.1
  • In a study of simeprevir in treatment-naive patients, sustained virologic response rates at week 12 (SVR12) were 58% in HCV genotype 1a patients with the NS3 Q80K polymorphism at baseline, compared to 84% SVR12 in patients without the Q80K polymorphism.1
  • The prevalence of the Q80K polymorphism in the United States is approximately 35% in genotype 1 overall and greater than 40% in genotype 1a.1
  • Prescribing information for simeprevir indicates that, “Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended.  Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism.”1

HCV GenoSure NS3/4A for Q80K Detection

The HCV GenoSure® NS3/4A Assay can be used to screen for the Q80K polymorphism in patients with HCV genotype 1. HCV GenoSure NS3/4A features include:

  • Assessment of HCV protease inhibitor susceptibility for boceprevir, simeprevir, and telaprevir.
  • Identification of amino acid variants within the nonstructural protein 3 (NS3) and 4A (NS4A) of HCV genotypes 1a and 1b.
  • Detection of mixtures of wild-type and drug-resistant variants when present at levels as low as 10% of the total population.
  • Use of the Monogram HCV genotypic interpretation database to derive a susceptibility assessment.