Journal
JOURNAL OF VIRAL HEPATITIS
Volume 19, Issue -, Pages 48-51Publisher
WILEY
DOI: 10.1111/j.1365-2893.2011.01526.x
Keywords
boceprevir; direct antiviral agents against hepatitis C; NS3; 4A protease inhibitors; NS5B polymerase inhibitors; telaprevir
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About half of the patients with chronic hepatitis C are still not cured by treatment with the current standard of care, peginterferon a/ribavirin. Direct antiviral drugs may overcome the limitations of standard antiviral therapy. The most promising new agents are inhibitors of the NS3/4A protease, the NS5B polymerase and the NS5A protein. Several compounds against these targets have entered clinical evaluation. Early clinical trials have emphasized the high potential for selecting resistant Hepatitis C virus variants. Furthermore, development of several new direct antivirals was stopped because of concerns over tolerability and safety. Then, in 2010, two phase III trials with the NS3/4A protease inhibitors boceprevir (SPRINT-2) and telaprevir (ADVANCE) showed that the combination of these compounds with standard care increases sustained virologic response rates in treatment-naive genotype 1 patients from 3844% to 6675%. Future goals of therapy with direct antiviral agents are to improve tolerability, shorten the duration of therapy and overcome the issue of resistance. Several studies have been initiated that combine different novel therapies, with and without interferon a/ribavirin.
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