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Resistance-Associated Substitution Testing Trends and Impact on HCV Treatment Outcomes in Canada: A CanHepC-CANUHC
Himain Perera1, Haris Imsirovic1, Gisela Macphail2
1Ottawa Hospital Research Institute, Ottawa, Canada.
Abstract:
Resistance-associated substitutions (RASs) are mutations within the hepatitis C (HCV) genome that may influence the likelihood of achieving a sustained virological response (SVR) with direct acting antiviral (DAA) treatment. Clinicians conduct RAS testing to adapt treatment regimens with the intent of improving the likelihood of cure. The Canadian Network Undertaking against Hepatitis C (CANUHC) prospective cohort consists of chronic HCV patients enrolled between 2015 and 2023 across 17 Canadian sites. Utilisation of RAS testing was assessed across demographics, clinical characteristics and years. SVR was described for the overall cohort and compared across populations of patients with historically negative predictors of SVR. The detection of key RASs and how this information influenced DAA selection were assessed. 2434 patients were identified with information on RAS testing. 98.3% achieved SVR. Out of the 227 patients tested for RAS, 147 (64.8%) had any detected RAS, and 84 (37.0%) had an NS5A RAS. The proportion of patients with SVR did not differ between RAS-tested (98.3%) and non-tested patients (98.3%; p = 0.99). SVR in those with an NS5a RAS was similar (98.6%) to the overall SVR proportion. Proportions with SVR did not differ between those with and without RAS testing in key subgroups (genotype 1a, genotype 3, prior treatment, cirrhosis). The specific DAA regimen and the addition of ribavirin were not associated with SVR outcome. RAS testing has a minimal influence on antiviral treatment selection. Going forward, there is a reduced role for RAS testing in most clinical scenarios.
Insights
Resistance-associated substitutions (RASs) testing in hepatitis C (HCV) patients did not significantly impact sustained virological response (SVR) rates with direct-acting antiviral (DAA) therapy. This suggests a limited role for RAS testing in guiding HCV treatment decisions.
Area of Science:
- Hepatology
- Virology
- Infectious Diseases
Background:
- Resistance-associated substitutions (RASs) are genetic mutations in the hepatitis C virus (HCV) genome.
- These mutations can affect the efficacy of direct-acting antiviral (DAA) treatments, influencing the achievement of sustained virological response (SVR).
- RAS testing is used to guide treatment selection and improve cure rates.
Purpose of the Study:
- To assess the utilization of RAS testing in a large Canadian prospective cohort of chronic HCV patients.
- To evaluate the impact of RAS testing on SVR rates across various patient demographics and clinical characteristics.
- To determine if RAS detection influences DAA selection and subsequent treatment outcomes.
Main Methods:
- Analysis of data from the Canadian Network Undertaking against Hepatitis C (CANUHC) prospective cohort (2015-2023).
- Assessment of RAS testing utilization across demographics, clinical factors, and enrollment years.
- Comparison of SVR rates between RAS-tested and non-tested patients, including subgroups with historically poor SVR predictors.
- Evaluation of the influence of detected RASs and treatment regimens on SVR outcomes.
Main Results:
- A total of 2434 patients were included; 98.3% achieved SVR.
- Of 227 patients tested for RAS, 64.8% had detectable RAS, and 37.0% had NS5A RAS.
- SVR rates were similar between RAS-tested (98.3%) and non-tested patients (98.3%).
- SVR rates in patients with NS5A RAS (98.6%) and in key subgroups (genotype 1a, genotype 3, prior treatment, cirrhosis) did not differ based on RAS testing status.
- Specific DAA regimens and ribavirin use were not associated with SVR outcomes.
Conclusions:
- RAS testing demonstrated a minimal influence on direct-acting antiviral treatment selection and SVR outcomes in this cohort.
- The study suggests a reduced clinical utility for routine RAS testing in most hepatitis C treatment scenarios.
- Future HCV treatment strategies may not require widespread RAS testing for optimizing patient cure rates.
