Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon-free direct-acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three-quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale-up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2-, 13-, and 15-fold increases, respectively). Scale-up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three-quarters within 15 years. Less impact occurs with delayed scale-up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US $3.2 million in Edinburgh and approximately $50 million in Melbourne and Vancouver. Conclusion: Interferon-free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale-up, and should be addressed. (Hepatology 2013;58:1598–1609)

investments to support countries with greatest burden of viral hepatitis All heavily burdened countries to have fully funded elimination plans by 2019 Recognition of need to focus on high burden countries and support for national policy development (All) Funding for national elimination plans Creation of fiscal space for new programmes with costed investment programmes Adopt domestic innovative finance tools where appropriate Support national policy makers in their activity (WHO, UNITAID, NGOs) Provide international support for financing measures (UNITAID, GFATM, bilaterial donors) Prevention Ensure all WHO elimination targets addressed in plans Address operational challenges in delivery of birth dose HBV vaccine Ensure provision of harm reduction services and engage with marginalised group (e.g. prisoners, PWIDs). Ensure clear public health messages to encourage testing and treatment Support countries to decriminalise injecting drug use and ensure equitable access to services for all (NGOs, WHO, civil society) Ensure appropriate funding for HBV vaccine, including birth dose (GAVI, WHO) Support R&D into HCV vaccine development (Research funders and pharma) Testing and Models of Care Focus on substantially scaling up testing for HBV and HCV Create and evaluate simplified care pathways relevant to local setting, integrating with existing services. Promote task sharing and decentralisation of care through capacity building, training and removal of Support operational research into simplified pathways (Research funders, UNITAID) requirements for specialised prescribing Diagnostics Ensure testing is integrated into the wider healthcare system, rather than centralised facilties Ensure access to quality diagnostics through Essential Diagnostic List and prequalification (WHO, funders) Support implementation science for models of care and R&D into novel diagnostics suitable for decentralised settings. (Research funders, FIND, industry) Access to treatment Ensure all Essential Medicines for viral hepatitis are included in national programmes, with an emphasis on pan-genotypic regimens Apply comprehensive policy approach to promoting access, including compulsory licensing Ensure all essential medicines are pre-qualified and either available through voluntary licensing or Medicines Patent Pool (WHO, NGOs, civil society, funders) Support shared procurement mechanisms for treatment (PAHO) Monitor Progress National plans need clearly defined, measurable objectives Develop new indices of national progress Progress of individual countries needs to be closely monitored towards elimination goals (Polaris, WHO, Creation of Elimination Index) Develop greater capacity for advocacy in high burden regions (all) Viral hepatitis is one of the leading causes of death in the world. 96% of those deaths are due to hepatitis B and C, which are the focus of this commission. Unlike many other major diseases, the tools exist to eliminate viral hepatitis. A highly effective vaccine is available to prevent hepatitis B, and a revolution in HCV treat...

Background. Interventions such as opiate substitution therapy (OST) and high-coverage needle and syringe programs (HCNSP) cannot substantially reduce hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV antiviral treatment may prevent onward transmission. We project the impact of combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among PWID.Methods. An HCV transmission model among PWID was used to project the combinations of OST, HCNSP, and antiviral treatment required to achieve different prevalence and incidence reductions within 10 years for 3 chronic prevalence scenarios and the impact of HCV treatment if only delivered through OST programs. Multivariate and univariate sensitivity analyses were performed.Results. Large reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral treatment. Scaling up OST and HCNSP substantially reduces the treatment rate required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage were increased to 40% each (no coverage at baseline), then annually treating 10, 23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60% baseline chronic HCV prevalences, respectively. Approximately 30% fewer treatments are necessary with new direct-acting antivirals. If coverage of OST and HCNSP is 50% at baseline, similar prevalence reductions require higher treatment rates for the same OST and HCNSP coverage.Conclusions. Combining antiviral treatment with OST with HCNSP is critical for achieving substantial reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are required on how best to scale up antiviral treatment and combine treatment with other interventions.