Heterogeneity in Risk and Implications for Hepatitis C Reinfection in People Who Inject Drugs in England.

Chronic hepatitis C virus (HCV) infection is associated with significant morbidity, mortality and health economic burden. Over 90% of HCV cases in England occur in people who inject drugs (PWID). Current treatments for HCV are effective but do not protect against reinfection. This research characterised HCV infection and reinfection risk in PWID in England using 2011-2021 data from the annual, cross-sectional, bio-behavioural survey of PWID, Unlinked Anonymous Monitoring. Risk factors for HCV infection were explored using multivariable logistic regression. Shared frailty models for the force of infection (FOI) were used to estimate the risk of HCV infection throughout injecting career with unmeasured risk variation modelled using gamma-shaped frailty distributions. HCV reinfection rates were derived using the frailty distributions of FOI models fitted to UAM data. Infection rates were highest in the first year of injecting (24 per 100 person-years) but fell to between 5 and 8 infections per 100 person-years subsequently. The estimated average annual risks of HCV primary infection and reinfection were 10.0% and 14.2%, indicating a 42% higher risk of reinfection compared to primary infection. Even those with no a priori risk factors were predicted to have high rates of reinfection if previously infected. These findings support the recognition of primary HCV infection as an independent risk factor for reinfection in PWID and emphasise the importance of reducing high-risk behaviours to prevent HCV reinfection following treatment of primary infection. Public health policies must recognise the importance of preventing reinfection in efforts to reduce HCV infection prevalence.