Moving beyond interferon alfa: investigational drugs for hepatitis C virus infection.
Numerous direct-acting drugs to treat hepatitis C virus (HCV) infection are in development, offering the potential for substantial improvement over current interferon alfa-based therapy and the possibility of effective interferon alfa-sparing regimens in achieving cure of HCV infection. Drugs furthest along in clinical development include HCV nonstructural protein 3 (NS3) protease inhibitors (eg, telaprevir, boceprevir), which have potent anti-HCV activity but low barriers to resistance and considerable likelihood of cross-resistance. Nucleoside analogue nonstructural protein 5B (NS5B) polymerase inhibitors exhibit a high barrier to resistance and cross-HCV genotype and subtype activity. Nonnucleoside analogue polymerase inhibitors have a low barrier to resistance and are characterized by a substantial frequency of preexisting resistance mutations. The initial use of direct-acting drugs will be as add-on treatment to interferon alfa and ribavirin regimens. The success of interferon alfa-sparing regimens will depend on presenting a sufficiently high barrier to resistance with direct-acting drugs and whether the immunomodulatory effects of interferon alfa are needed for cure of HCV infection.
University of California San Diego, La Jolla, CA, USA.
David L
DL
Wyles
D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D009705:Nucleosides / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D009705:Nucleosides; D011480:Protease Inhibitors