Interpretation

HCV infection is the most common
chronic bloodborne infection in the U.S., with approximately 3.2
million people chronically infected and an additional 17,000
(approx.) new infections acquired annually. Multiple drugs approved
to treat HCV target the NS5A protein.
Specific mutations in these genes have been implicated in
resistance to various HCV antiviral drugs
including: daclatasvir (Daklinza®), elbasvir (in
Zepatier®), ledipasvir (in Harvoni®), ombitasvir (in
Viekira Pak®, Viekira XR® and Technivie®), pibrentasvir
(in Mavyret®), and velpatasvir (in Epclusa® and
Vosevi®). Multiple mutations causing resistance to these
FDA-approved HCV inhibitors have been defined, and the levels of
increased resistance for each mutation have been calculated using
HCV replicons or reporter constructs.
Some of the mutations cause resistance to multiple NS5A inhibitors.
Knowledge of these mutations is important in patients since an
incomplete suppression of viral replication by an ineffective drug
combination could prevent a sustained viral response
(“cure”), and could readily support the development of
antiviral drug resistance.