The “modern” era of hepatitis C virus (HCV) treatment began in 2014 with FDA approval of the direct acting antiviral agent (DAA) Harvoni for use in HCV monoinfected patients. Since then, the FDA-approved indication of Harvoni has been expanded to include the HCV/HIV co-infected population and the FDA has approved 5 more DAAs or combinations of DAAs.
Treatment Regimens Target Proteins
The development of multiple DAAs, which target specific steps within the HCV life cycle, has been facilitated by knowledge of the HCV genome and proteins. The current treatment regimens target proteins that are involved in HCV replication and assembly, such as NS3/4A protease, NS5B polymerase, and the NS5A protein. Combination therapy is used to optimize HCV treatment response rates and reduce the likelihood of developing treatment-emergent resistance-associated variants.
Following are the 4 classes of DAAs:
1. NS3/4A protease inhibitors: grazoprevir (a component of Zepatier™), paritaprevir (a component of Technivie™ and Viekira Pak™), and simeprevir (Olysio™).
2. NS5A inhibitors: daclatasvir (Daklinza™), elbasvir (a component of Zepatier™), ledipasvir (a component of Harvoni™), ombitasvir (a component of Technivie™ and Viekira Pak™), and velpatasvir (a component of Epclusa™).
3. NS5B nucleot(s)ide polymerase inhibitors: sofosbuvir (Solvaldi™ and a component of Harvoni™).
4. NS5B non-nucleoside polymerase inhibitors: dasabuvir (a component of Viekira Pak™).
Compensated or Decompensated Cirrhosis?
Duration of treatment is based on genotype, prior treatment history, and the presence of compensated or decompensated cirrhosis. These types of cirrhosis may be distinguished by noting that persons with compensated cirrhosis do not have hepatic encephalopathy, ascites, variceal bleeding, or jaundice. Treatment of patients with decompensated cirrhosis or those with hepatocellular carcinoma should be deferred to a specialist.
Persons who are co-infected with HIV and hepatitis B virus probably should be referred to an infectious diseases specialist or to a hepatologist.
American Association for the Study of Liver Diseases and Infectious Diseases Society of America. Recommendations for Testing, Managing, and Treating Hepatitis C.