The global burden of hepatitis C virus (HCV) infection continues to rise.[1, 2] The core of the HCV epidemic in the developed world occurs among people who inject drugs (PWID), who comprise the majority of new (80%) and existing (60%) cases. Globally, HCV seroprevalence (>60% in most countries) and incidence (5%-40% annually)[4, 5] remains high among PWID. Prevention strategies, such as needle and syringe programs (NSP) and opiate substitution therapy (OST), can reduce HCV transmission and have maintained low levels of human immunodeficiency virus (HIV) infection in many settings, but they are insufficient to achieve substantial reductions in HCV prevalence.[6-9] This is partly because high HCV prevalence and long injecting duration among PWID in many settings combine such that the intervention coverage required for major prevalence reductions is unobtainable and unsustainable. Given that there is no HCV vaccine, alternative strategies for HCV prevention are urgently needed.
In HIV, the demonstration that antiretroviral therapy given to HIV-infected individuals can prevent secondary transmission has generated considerable excitement and suggests that we may have reached a tipping point for preventing HIV transmission. In contrast to HIV, HCV is curable and therapy is finite. Therefore, HCV treatment as prevention may provide even greater opportunity for preventing onward HCV transmission and directly reducing HCV chronic prevalence.
Mathematical modeling studies have suggested HCV treatment for PWID could be an effective[12-16] and cost-effective intervention to prevent HCV transmission. However, these studies only considered treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). The feasibility of expanding this treatment regimen as a strategy for treatment as prevention is limited, given the poor tolerability and limited uptake of PEG-IFN+RBV therapy, particularly among PWID.[18, 19] However, therapeutic options for HCV are evolving rapidly. Preliminary data from IFN-free direct-acting antiviral (DAA) therapy phase 2 trials indicates that in the near future, regimens will be available with markedly reduced toxicity, high efficacy (>90% cure), improved dosing schedules (once or twice-daily), and shortened treatment duration (6-24 weeks).[20-22] Such advances indicate that a HCV treatment as prevention strategy among PWID may be feasible in the very near future.
We project the potential impact of DAA therapy on HCV prevalence in three international settings with varied prevalence.