Cedars-Sinai Medical Center, Los Angeles, CA, USA.
BACKGROUND & AIMS:
Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors.
Previously untreated patients (from the SPRINT-2 trial) and those that did not respond to prior therapy (from the RESPOND-2 trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration 28-48 weeks). A good response to interferon was defined as a ≥1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a <1 log(10) decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism IL -28B rs12979860) associated with response. The polymorphism IL -28B rs8099917 was also assessed.
In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR]=11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs=2.6 and 2.1), absence of cirrhosis (OR=4.3), HCV subtype 1b (OR=2.0), and non-black race (OR=2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous non-response (OR=2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was more strongly associated with a good response to interferon than other baseline factors; however, a ≥1 log(10) decrease in HCV RNA at week 4 was more strongly associated with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR.
The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥1 log(10) decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B.