title: Hepatitis C: recent successes and continuing challenges in the development of improved treatment modalities.
abstract: Dramatic progress is being made toward the development of less-toxic and simpler alternatives to the current standard-of-care therapy for chronic hepatitis C, which involves a combination of pegylated interferon (peg-IFN) and ribavirin (RBV). Several accessible viral targets have been identified and licensure of the most advanced clinical compounds can be anticipated within the next several years. However, the highly replicative nature of HCV infection, coupled with error-prone viral RNA synthesis and considerable genome diversity, pose extraordinary challenges to drug development. Peg-IFN is likely to remain a mainstay of therapy for the foreseeable future, or until such time that multiple direct-acting antiviral (STAT-C) inhibitors are available and shown to provide a sufficiently high barrier to resistance when used in combination.
authors.affiliation: Center for Hepatitis Research, Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shimakami
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lanford
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons