What is the role of NS3/4 serine protease inhibitors in the treatment of hepatitis C (hep C) infection?

Updated: Oct 07, 2019
  • Author: Vinod K Dhawan, MD, FACP, FRCPC, FIDSA; Chief Editor: BS Anand, MD  more...
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Answer

These agents target the NS3/4 serine protease to inhibit HCV replication. In 2011, boceprevir and telaprevir were approved to treat genotype 1 HCV infection. However, treatment with these two agents is no longer recommended and they have been discontinued from the market. Their use has been superseded by the more recently approved protease inhibitors active against a broader range of viruses.

Simeprevir was approved by the FDA for the treatment of HCV genotype 4 monoinfected and HCV/human immunodeficiency virus (HIV)-coinfected patients as a component of a combination antiviral treatment regimen that includes PEG-IFN and ribavirin. [104]

Paritaprevir given in combination with ritonavir and ribavirin to patients with hepatitis C genotype 1 for 12 weeks resulted in an SVR of 95% at 24 weeks after treatment discontinuation. [105] Paritaprevir is a component of Viekira Pak and Technivie as discussed previously.

Grazoprevir is active against a range of HCV genotypes, including some that are resistant to the most currently used antiviral medications. It is used in combination with the NS5A replication complex inhibitor elbasvir under the trade name Zepatier, either with or without ribavirin.

Asunaprevir, another agent in this class, is currently not available in the United States.


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