What is the role of protease inhibitors in the treatment of hepatitis C virus (HCV) infection?

Updated: Dec 09, 2020
  • Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: Michael Stuart Bronze, MD  more...
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In May 2011, the HCV NS3/4A protease inhibitors boceprevir and telaprevir received FDA approval for patients infected with HCV genotype 1. However, treatment with either of these agents is no longer recommended because of the higher efficacy and improved safety profile of other regimens. The sale and distribution of telaprevir was discontinued in the United States in 2014. The sale and distribution of boceprevir was discontinued in the United States in 2015.

A third protease inhibitor, simeprevir, received FDA approval in November 2013 for use in patients infected with HCV genotype 1. Initial approval specified that simeprevir (now discontinued in the United States) be used in combination with peginterferon and ribavirin in patients with compensated liver disease. However, the naturally-occurring NS3/4A Q80K amino acid substitution was problematic for patients with genotype 1a. This resistance-associated variant (RAV) was seen in about 30% of patients with genotype 1a infection. If present, the polymorphism was associated with a lower SVR in simeprevir-treated patients. SVR rates in previously untreated patients were reported as 84% in genotype 1a patients without the Q80K polymorphism, 58% in genotype 1a patients with the Q80K polymorphism, and 85% in genotype 1b patients. [10] Accordingly, it was recommended that patients with genotype 1a and the Q80K polymorphism not receive combination therapy with peginterferon, ribavirin, and simeprevir.

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