Effect of drug-resistance mutations on antiviral agents in HCV patients.

Background: Gene polymorphism of HCV is an important cause of drug resistance to direct-acting antivirals (DAAs). Methods: Nested PCR assays were performed to amplify the HCV viral regions of NS3, NS5A and NS5B. Results: Major resistant mutation A156S was found in 18.33% of patients with HCV-1b and 64.28% of patients with HCV-2a. HCV-6a patients had a Q80K mutation rate of 95.45%, while the mutation rate of V170I was up to 100%. Mutation frequency varied with the different genotypes of HCV. The proportion of four resistance mutations (M36L, Q80K, A156S, V170I) in different groups were statistically significant (P< 0.05). Resistant mutation Q30R was detected in 116 (72.5%) samples with HCV-1b and -6a, L31M was found in 16 patients, including 12 with HCV-2a and 4 with HCV-6a, H58P was discovered in 42.5% (68/160) of patients with the genotypes Q30R, L31M and H58P; Y93C was found in 9-individuals with only HCV-2a. In HCV NS5B sequences, only a few resistant variants were detected, including C316N and S282T. Conclusions: Naturally occurring dominant resistance mutations to HCV DAAs pre-existed in treatment-naive patients in China. Mutation frequency and characteristics varied with the HCV genotype.