Direct-acting antiviral treatment outcomes in people infected with endemic compared to epidemic hepatitis C virus subtypes in England

Background

Current evidence suggests reduced efficacy of direct-acting antiviral (DAA) treatment among people with endemic Hepatitis C virus (HCV) subtypes rare to high-income countries. We aimed to determine real-world DAA treatment outcomes of people with endemic HCV subtypes in England.

Methods

Data were collected through a national treatment program. People who had their virus subtyped between 2019–2023, were resident in England and had an outcome recorded for their first DAA treatment episode, were included. Subtypes were divided into epidemic and endemic in England; endemic subtypes were confirmed with whole genome sequencing and resistance associated substitutions (RAS) were determined. Logistic regression was used to determine associations between treatment outcome and exposure variables.

Results

In people with an outcome recorded, 93 with an endemic and 8671 with an epidemic HCV subtype were identified, of whom 49.5% (46/93) and 91.8% (7953/8668) achieved a sustained virological response at 12 weeks post end of DAA treatment (SVR12), respectively. In the multivariable model, people with an endemic subtype had 93% (aOR 0.07 95%CI 0.04–0.12, P=<0.001) reduced odds of achieving SVR12. Treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir was successful for genotypes 1, 2, 4 and 5 (SVR12 100%, n=13) but not 3 (27.3%, n=22) endemic subtypes. Sofosbuvir/velpatasvir/voxilaprevir was successful for GT3 endemic subtypes at retreatment (SVR12 11/12, 91.7%). Treatment failures for genotypes 1, 3 and 4 were likely mediated by naturally occurring baseline NS5A RAS (median n=2).

Discussion

This study provides further evidence that endemic HCV subtypes lead to sub-optimal DAA efficacy, which may impact global HCV elimination.