Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective

Abstract

Until very recently, treatment for chronic hepatitis C virus (HCV) infection has been based on the combination of two non-viral specific drugs: pegylated interferon-α and ribavirin, which is effective in, overall, about 40%-50% of cases. To improve the response to treatment, novel drugs have been designed to specifically block viral proteins. Multiple compounds are under development, and the approval for clinical use of the first of such direct-acting antivirals in 2011 (Telaprevir and Boceprevir), represents a milestone in HCV treatment. HCV therapeutics is entering a new expanding era, and a highly-effective cure is envisioned for the first time since the discovery of the virus in 1989. However, any antiviral treatment may be limited by the capacity of the virus to overcome the selective pressure of new drugs, generating antiviral resistance. Here, we try to provide a basic overview of new treatments, HCV resistance to new antivirals and some considerations derived from a Public Health perspective, using HCV resistance to protease and polymerase inhibitors as examples.

Keywords: Direct-acting antiviral; Polymerase inhibitors; Protease inhibitors; Specifically-targeted antiviral therapy; Viral resistance.

Figure 1

Diagram of the hepatitis C virus genes and the viral polyprotein, with two non-coding regions in the 5’ and 3’ ends of the viral genome, structural (with) and non-structural (grey) proteins. The targets for the most-developed Specifically-Targeted Antiviral-Treatment for hepatitis C compounds are indicated, together with drugs in advanced development.