Concise Review Hepatitis C Virus Resistance to Antiviral Therapy

Research produces highly efficient antiviral drugs. At the same time, viruses develop sophisticated strategies to evade their actions. Resistance to antiviral therapy has become a major issue in the management of patients with chronic viral infections. The best known example is human immunodeficiency virus (HIV), but cytomegalovirus, herpes simplex virus, and hepatitis B and C viruses exhibit similar capabilities. About 60% of patients with chronic hepatitis C do not clear hepatitis C virus (HCV) infection with the currently approved therapeutic regimen and are considered “resistant” to therapy. The resistance of HIV to antiretroviral drugs has often been used as a model for HCV resistance. However, the two drugs currently used in the treatment of HCV, interferon alfa (IFN-a) and ribavirin, have complex and indirect actions, making the mechanisms of HCV resistance generally different from those of viral resistance to specific antiviral agents. Molecular mechanisms of resistance to IFN-based therapy have recently been proposed on the basis of in vitro experiments but have not been validated in patients, in whom treatment failure appears to be multifactorial. The aim of this review is to clarify what is known, what is hypothesized, and what remains unknown in the field of HCV resistance to IFN-based antiviral therapy.