Patients with HCV genotype-1 who have failed a direct-acting antiviral regimen: virological characteristics and efficacy of retreatment

Antivir Ther. 2019;24(7):485-493. doi: 10.3851/IMP3296.


Background: This real-world clinical setting study characterized the virological patterns in genotype-1 patients failing interferon (IFN)-free regimens and evaluated the efficacy of re-treatment.

Methods: A total of 73 consecutive patients failing IFN-free regimens were enrolled (17 genotype-1a and 56 -1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols.

Results: In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype-1a than in the 24 with genotype-1b (80% versus 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype-1a and the 27 with genotype-1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype-1b than in the 10 with genotype-1a (37.7% versus 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype-1a and 45.5% in the 11 with genotype-1b. The 6 patients re-treated with genotype-1a less frequently (50%) showed sustained virological response (SVR) than the 18 with genotype-1b (88.8%; P=0.07). SVR was more frequent in the 21 patients with an effective second-line direct-acting antiviral (DAA) regimen than the 3 without (90.4% versus 0%; P<0.005).

Conclusions: The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / classification
  • Antiviral Agents / therapeutic use*
  • Female
  • Genotype*
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology*
  • Humans
  • Male
  • Middle Aged


  • Antiviral Agents