Pre-treatment antiviral resistance in Australians with chronic hepatitis C: prevalence of NS3 and NS5A resistance data in the state of New South Wales.

Abstract

Direct-acting antivirals (DAAs) have revolutionized HCV treatment, but the impact of antiviral resistance at a population level is still not clear. The majority of patients who fail DAA therapy develop resistance-associated substitutions (RASs), which can impact re-treatment. There is potential for resistance prevalence to rise in the community with treatment scale up, due to transmission of resistant virus. Monitoring for increasing antiviral resistance requires a reliable baseline, yet there are few published data on the prevalence of HCV resistance in Australia. The aim of this study was to determine the prevalence of RASs among untreated Australians with HCV genotype-1a infection, to inform ongoing surveillance. A cross-sectional study was performed at a single large university hospital pathology laboratory in Australia. Archived blood samples referred for HCV genotype testing were analysed. All patients were naive to DAAs. The prevalence of RASs in the HCV NS3 and NS5A regions was determined using Sanger based population sequencing. Of 379 samples tested, 34% contained DAA-resistant virus: 24% had resistance to NS3 protease inhibitors, 12% had NS5A inhibitor resistance and 4% of patients had resistance to both drug classes. Clinically relevant RASs conferring resistance against NS5A inhibitors ledipasvir, daclatasvir and elbasvir were detected in 5.8% of samples. This is the largest study of HCV antiviral drug resistance in Australia, which differs from resistance prevalence in the USA. The results provide valuable data on the baseline prevalence of HCV resistance, which can be used in the future to monitor for increasing antiviral resistance.