A new standard of care for the treatment of chronic HCV infection

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Abstract

The introduction of direct acting antiviral agents (DAAs) will markedly change treatment options for individuals who have a chronic HCV infection. Within the next few months, licensing of two HCV protease inhibitors (boceprevir and telaprevir) for the treatment of patients with chronic hepatitis C as part of a triple therapy with PEG-IFN-α and ribavirin is anticipated in the USA, Europe and many other countries. Final results of pivotal phase III clinical trials in previously untreated and treatment-experienced patients with HCV genotype 1 infection were presented at the Annual Meeting of the American Association for the Study of the Liver 2010 held in Boston, MA, USA, and at the Annual Conference of the Asian Pacific Association for the Study of the Liver 2011, held in Bangkok, Thailand. This article summarizes the results of these phase III trials in consideration of accumulating data on important baseline and on-treatment predictive factors for treatment response, such as the host IL28B genotype and the rapid virologic response; the introduction of these new therapies into clinical practice is also covered. Furthermore, preliminary data on the combination of different classes of DAAs, such as HCV protease inhibitors and HCV polymerase inhibitors, without interferon α are discussed.

Key Points

  • Among host and viral factors associated with sustained virologic response, the IL28B genotype and rapid virologic response (RVR) have the strongest predictive value; RVR is crucial to response-guided therapy

  • Response-guided therapy aims to shorten treatment regimens in previously untreated patients; 44% and 57–65% of patients treated with boceprevir and telaprevir, respectively, qualified for shortened treatment

  • Patients with HCV genotype 1 infection and previous treatment failure benefit from triple therapies containing boceprevir or telaprevir, but most require an extended total treatment duration (up to 48 weeks)

  • The selection of HCV variants that have decreased susceptibility to direct acting antiviral agents might occur during treatment and is associated with virologic breakthrough and treatment failure

  • When administering combination therapy, careful monitoring of viral load and stringent futility rules should be used to prevent the development of multiresistant HCV strains

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Figure 1: Final SVR results of the SPRINT-2 trial in two populations of previously untreated patients infected with HCV genotype 1 (nonblack and black patients).
Figure 2: Final SVR results of the ADVANCE study in previously untreated patients infected with HCV genotype 1.
Figure 3: Final SVR results of the ILLUMINATE study.
Figure 4: Final SVR results of the RESPOND-2 study in patients infected with HCV genotype 1 who failed previous treatment.
Figure 5: SVR results of the REALIZE study in patients infected with HCV genotype 1 who failed previous antiviral treatment.

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Acknowledgements

W. P. Hofmann and S. Zeuzem receive funding from the Deutsche Forschungsgemeinschaft (grant KFO129).

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Both authors contributed equally to all aspects of this article.

Correspondence to Stefan Zeuzem.

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Competing interests

W. P. Hofmann has been a speaker for Bristol-Myers Squibb, Gilead, Merck and Roche, and has received grant/research support from Roche. S. Zeuzem has been a consultant for Abbott, Achillion, Anadys, Bristol-Myers Squibb, Gilead, Itherx, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec and Vertex. S. Zeuzem has been a speaker for Bristol-Myers Squibb, Gilead, Merck, Novartis and Roche.

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Hofmann, W., Zeuzem, S. A new standard of care for the treatment of chronic HCV infection. Nat Rev Gastroenterol Hepatol 8, 257–264 (2011) doi:10.1038/nrgastro.2011.49

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