Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients

Abstract

Background: Direct-acting antiviral (DAA) resistance-associated substitutions (RASs) can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV). The selection pressure by pegylated-interferon (Peg-IFN) plus ribavirin (P/R) treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT) 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group) and those previously treated with P/R (post-IFN group). The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]). The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%). The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%-5%). Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not favorably associated with an increase in DAAs RASs present in GT1a patients. Our results support the American Association for the Study of Liver Diseases’ recommendations of DAA intervention in P/Rtreated GT1a patients.