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Protease Inhibitor Resistance

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Handbook of Antimicrobial Resistance

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Abstract

The recent development of hepatitis C virus (HCV)–specific direct-acting antivirals (DAAs) has marked a major milestone in the treatment of chronic HCV infection, allowing for viral elimination in the majority of treated patients. The first two drugs to be approved for the treatment of HCV genotype 1 infection were the HCV NS3/4A protease inhibitors telaprevir and boceprevir. However, their administration in combination with pegylated interferon alfa and ribavirin was associated with poor tolerability despite showing improved overall efficacy. In addition, as in DAAs targeting other viruses, concerns were raised with regard to the selection of drug-resistant viral variants. Selection of resistance-associated variants (RAVs) allows the virus to escape from drug pressure with subsequent treatment failure. The emergence of RAVs depends on a number of drug-, host-, and virus-related factors that are reviewed here. In addition, detailed resistance profiles of approved protease inhibitors and those that are still in clinical development are also discussed.

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Authors and Affiliations

  1. Medizinische Klinik 1, Universitätsklinikum, Frankfurt, Germany

    Johannes Vermehren, Christoph Welsch & Christoph Sarrazin

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  1. Johannes Vermehren
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  2. Christoph Welsch
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  3. Christoph Sarrazin
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Correspondence to Johannes Vermehren .

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Editors and Affiliations

  1. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Albert Berghuis

  2. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Greg Matlashewski

  3. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Mark A. Wainberg

  4. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Donald Sheppard

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Vermehren, J., Welsch, C., Sarrazin, C. (2017). Protease Inhibitor Resistance. In: Berghuis, A., Matlashewski, G., Wainberg, M., Sheppard, D. (eds) Handbook of Antimicrobial Resistance. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0694-9_6

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