Therapeutic implications of hepatitis C virus resistance to antiviral drugs.

Treatment of chronic hepatitis C is currently based on a combination of pegylated interferon-o! and ribavirin. Neither drug exerts direct selective pressure on viral functions, meaning that interferon-a/ribavirin treatment failure is not due to selection of interferon-a- or ribavirin-resistant viral variants. Several novel antiviral approaches are currently in preclinical or clinical development, and most target viral enzymes and functions, such as hepatitis C virus protease and polymerase. These new drugs all potentially select resistant viral variants both in vitro and in vivo, and resistance is therefore likely to become an important issue in clinical practice.