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lüll Moving beyond interferon alfa: investigational drugs for hepatitis C virus infection Wyles DLTop HIV Med 2010[Oct]; 18 (4): 132-6Numerous 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.|Antiviral Agents/*therapeutic use[MESH]|Drug Resistance, Viral[MESH]|Drug Therapy, Combination[MESH]|Hepatitis C/*drug therapy[MESH]|Humans[MESH]|Interferon-alpha/therapeutic use[MESH]|Nucleosides/therapeutic use[MESH]|Protease Inhibitors/therapeutic use[MESH]|Treatment Outcome[MESH] |