The natural history of HCV with an increase in liver cirrhosis after 15-20 years and an ageing cohort of people who inject drugs (PWID) means that a large burden of advanced liver disease is anticipated in the next decade. Further, HCV transmission continues to occur among PWID. Targeted treatment to those potentially at higher risk of transmission could potentially be used to inform strategies for the implementation of public health and treatment-as-prevention interventions at a population level.
Despite revised guidelines, few PWID have received HCV treatment.Enhanced HCV assessment and treatment in PWID will be required to reduce future HCV-related morbidity and mortality.
Treatment of chronic HCV with pegylated interferon-alfa (PEG-IFN)/ribavirin is safe and effective among those with a history of injecting drug use (IDU) and among active PWID, with 54-56% attaining a sustained virological response (SVR). However, the majority of studies in this area have been limited by small sample sizes and retrospective study designs.
ACTIVATE is an international network of 17 sites across seven countries with experience in the treatment of HCV infection among PWID. The ACTIVATE study is a phase IV, open-label, multicentre, international trial of response guided treatment with directly observed pegylated interferon alfa 2b and self-administered ribavirin for patients with chronic HCV genotype 2 or 3 infection and recent injection drug use or receiving OST. However, therapy with PEG-IFN and ribavirin is associated with considerable side-effects, complicating therapy among PWID.
The Gilead Sciences IFN-free dual DAA regimen of sofosbuvir 400 mg once-daily (SOF, nucleotide polymerase inhibitor) and GS-5816 100 mg once-daily (NS5A inhibitor) has demonstrated high efficacy (95-96% SVR12) with a treatment duration of 12 weeks in treatment-naïve patients with HCV genotypes 1-6 and is currently in phase III evaluation as a 12 week regimen. The availability of a simplified IFN-free DAA-based once-daily regimen of sofosbuvir/GS-5816 should considerably enhance the capacity to scale-up HCV treatment among PWID.