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Hepatitis C virus (HCV) infection is costly to treat and, has high morbidity and mortality. The addition of new protease inhibitors (i.e., boceprevir, telaprevir), to the standard dual therapy with pegylated interferon-α and ribavirin, for the treatment of HCV infection has demonstrated superior efficacy with shorter treatment duration, but at higher drug acquisition costs and incidence of adverse events. Robust economic data are required to inform healthcare decision for the optimal use of these expensive antiviral agents. Accordingly, this review will explore the clinical and economic aspects of boceprevir-based treatment strategies. Important considerations, challenges and gaps for future pharmacoeconomic research in this setting are highlighted.