Transmission and treatment of hepatitis C virus infection in people who inject drugs

Background: The advent of novel, highly efficacious, and well tolerated hepatitis C virus (HCV) therapies could potentially lead to the elimination of HCV in many settings globally. A better understanding of HCV transmission and treatment among people who inject drugs (PWID) is needed for this potential to be realised. Aims: The broad aim of this research was to inform prevention and treatment of HCV infection in PWID. Specific aims included the evaluation of injecting risk behaviours and incidence of HCV infection among PWID in an Australian prison setting; to investigate HCV transmission via phylogenetic analyses in a population of street-involved youth in Vancouver, Canada; and to evaluate adherence to pegylated interferon/ribavirin therapy and sofosbuvir/velpatasvir therapy among PWID.Methods: In Chapter 2 and Chapter 3, data from the HITS-p study were analysed using Cox proportional hazard, logistic regression, and generalized estimating equation (GEE) methodologies. In Chapter 4, data from the At-Risk Youth Study (ARYS) were analysed using maximum likelihood phylogenetic and logistic regression methods. In Chapter 5 and 6, adherence and behavioural data from the ACTIVATE and SIMPLIFY studies were analysed using GEE and logistic regression methodologies. Key findings: In the HITS-p study, primary HCV infection was associated with needle/syringe sharing irrespective of injecting frequency or drug type. The incidence was high and remained stable between 2005 and 2014. Needle/syringe sharing increased following entry into prison while any injecting drug use decreased. Younger age was associated with continuing and reinitiating injecting following prison entry as well as ongoing injecting risk behaviours while in prison. Methamphetamine injecting was associated with phylogenetic clustering in street-involved youth. PWID demonstrated high adherence to both PEG-IFN/RBV and sofosbuvir/velpatasvir. Injecting cocaine or amphetamines was associated with reduced adherence to sofosbuvir/velpatasvir however any injecting at baseline was not associated with overall adherence to therapy.Conclusion: A multifaceted approach is needed to effectively reduce the prevalence and incidence of HCV infection among PWID. Scale up of HCV prevention strategies including needle and syringe programs and opioid substitution therapy are needed to supplement the scale up of DAA therapy to provide the greatest prevention benefit to meet global HCV elimination targets