Insight Into Resistance-Associated Substitutions May Guide HCV Retreatment

Point mutation
Point mutation
Specific resistance-associated substitutions may occur after DAA treatment failure.

Daclatasvir plus asunaprevir (DCV+ASV) treatment is a direct-acting antiviral (DAA) therapy for patients with genotype 1b hepatitis C virus (HCV), and findings from a new study published in the Journal of Viral Hepatitis may help further the understanding of the emergence and persistence of resistance-associated substitutions (RASs).

The development of RASs is an important issue when treatment options are being considered, and identifying RASs after initial treatment failure warrants further consideration when the retreatment options are being considered.

The study cohort included 363 patients chronically infected with genotype 1b HCV who were started on 24 weeks of treatment with DCV+ASV.

HCV was analyzed in patients who did not respond to treatment, and the sequences of both NS5A and NS3 were conducted after treatment failure.

The investigators found that RASs of NS3 reverted to the wild-type amino acid within 1 year following treatment failure but the RASs of NS5A remained stable and did not change.

The effect of trans-complementation of NS5A was also observed after co-transfection investigations and these findings suggest that “such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment.”

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“Depending on the presence of RASs in NS3, the choice would be a combination of DAAs inhibiting NS5B polymerase only (both nucleotide inhibitor and non-nucleoside inhibitor) or a combination of DAAs inhibiting both NS5B polymerase and NS3 protease,” the study investigators concluded.


Jeong Y, Jin B, Lee HW, et al. Evolution and persistence of the resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures [published online May 16, 2018]. J Viral Hepat. doi:10.1111/jvh.12932