P129 People infected with ‘rare’ genetic subtypes of hepatitis C virus have lower sustained viral response rates to treatment with direct acting antiviral therapy compared to those infected with ‘common’ subtypes, in NHS England

Background

The UK is committed to the WHO target to eliminate Hepatitis C virus (HCV) as a public health threat by 2030. This is achievable due to the success of direct-acting antiviral (DAA) treatment which has contributed to a 47% reduction in HCV infections between 2015 and 2021. The HCV virus is extremely diverse with eight genotypes and over 100 subtypes currently defined. Despite this, most clinical trials of DAA efficacy include a small subset of these subtypes, prevalent in high-income countries, with highly diverse subtypes ‘rare’ to the UK remaining significantly under-represented. Current limited evidence suggests much lower treatment success rates among these ‘rare’ subtypes, which is likely to impact progress towards elimination. We aimed to determine the real-world outcomes of DAA therapy for treatment of HCV subtypes ‘rare’ to the UK.

Methods

Datasets collected as part of the NHS England treatment program delivered by HCV Operational Delivery Networks between 2018 and 2022 were interrogated to ascertain the outcome for first course of DAA treatment. Those who did not reach treatment end were removed, including: ‘not completed’, ‘lost to follow up’, ‘death prior’, and ‘other’. Genotypes 1a, 1b, 2b, 3a, 4a and 4d were defined as common subtypes (n=7274), and any other subtype was defined as ‘rare’ subtypes to the UK (n=84). Whole genome sequencing was used to confirm all ‘rare’ subtype samples. Multivariate logistic regression was used to assess treatment outcome in ‘rare’ and ‘common’ subtypes using R (GNU General Public License v4.1.2).

Results

Sustained virological response at 12 weeks after end of DAA therapy (SVR12) were achieved in 54% of ‘rare’ and 92% of ‘common’ subtype infections (45/84 vs 6671/7274). Additionally, people infected with ‘rare’ subtypes were more likely than those with ‘common’ subtypes to experience relapse (31% vs 3%), non-response (10% vs 2%) and viral breakthroughs (6% vs 0%) (figure 1). After adjustment for potential confounders, the decrease in the odds of achieving SVR12 with a ‘rare’ HCV subtype was 91% (95%CI: 84%-94%) compared to a ‘common’ subtype (p<0.001).

Discussion

In conclusion, infection with a ‘rare’ HCV subtype resulted in a significantly reduced odds of achieving SVR12, compared to a ‘common’ subtype infection. This work supports current evidence suggesting ‘rare’ HCV subtype infections lead to sub-optimal DAA efficacy, which may result in increasing relative prevalence of harder to treat HCV infections, impacting our ability to achieve HCV elimination in the UK and globally.