In the treatment of the hepatitis C virus (HCV), it should come as no surprise that resistance-associated variants (RAVs)—pre-existing or selected during treatment—would limit the activity of some drugs. After all, there is a wealth of knowledge about the importance of baseline, transmitted, and regimen-selected resistance mutations after the almost 30 years antiretroviral drugs have been available to treat HIV.
An HIV Lesson Learned
In fact, one of the principles of treating HIV infection is to use drugs from at least 2 classes, both to increase the potency of the treatment regimen and to make resistance less likely to develop during the course of therapy. Of course, the “modern” era of treating HCV with the direct acting antiviral agents is only about 2 years old. Consequently, only recently have we begun to appreciate the role resistance plays in HCV treatment.
FDA-approved HCV Drugs and Drug Combinations
The 8 drugs or drug combinations that are FDA approved to treat patients with HCV fall into the following 4 classes:
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™).