Telaprevir: changing the standard of care of chronic hepatitis C

Abstract

Chronic hepatitis C is a major public health problem and its burden is expected to increase in the near future. Out of six genotypes of hepatitis C virus (HCV) identified, genotype 1 is the most prevalent genotype in America and Europe. With peg-interferon alpha and ribavirin dual therapy, sustained virological response (SVR) is achieved in less than half of the patients infected with HCV genotype 1. Moreover, this dual therapy also causes many intolerable adverse effects. Telaprevir is an HCV protease inhibitor approved for chronic hepatitis C genotype 1 mono-infection. It is a type of direct acting antiviral drug acting through inhibition of viral non-structural 3/4A protease. It can be safely administered in mild hepatic dysfunction. Due to inhibition of CYP3A4 and P-glycoprotein, significant drug-drug interactions are possible with telaprevir. Trials have shown significantly higher SVR rates when telaprevir is added to peg-interferon alpha and ribavirin, particularly in patients with unfavorable prognostic factors. It is approved for use in treatment-naïve and previously treated patients. Rash and anemia are the major troublesome side-effects. Next-generation protease inhibitors may overcome the drawbacks of telaprevir and another approved HCV protease inhibitor - boceprevir. Evidence from small scale studies suggests that telaprevir may be used in conditions like HIV co-infection, post-transplantation and some HCV non-1 genotype infections also. Preliminary data show higher SVR rates with triple therapy even in patients with unfavorable interleukin-28B (IL28B) genotype. With development of other direct acting antivirals, it might be possible to treat chronic hepatitis C with interferon-free regimens in future. This article briefly reviews the properties of telaprevir and its status in the context of rapidly evolving aspects of management of chronic hepatitis C.