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. The HCV NS3 serine protease plays a critical role in
viral pathogenesis and serves to cleave the viral polyprotein at
several points, releasing the component viral proteins. Multiple
mutations causing resistance to FDA-approved HCV protease
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 protease
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. In addition to detection
of drug resistance during treatment, a screen for the protease Q80K
variant in subtypes 1a is recommended prior to the use of
simeprevir. The manufacturer’s package insert for the
protease inhibitor simeprevir (Olysio®) states as follows:
“Screening patients with HCV
genotype 1a infection for the presence of virus with the NS3 Q80K
polymorphism at baseline is strongly recommended. Alternative
therapy should be considered for patients infected with
HCV genotype 1a containing the Q80K
polymorphism.”