studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 555A
in phase 2/3 trials of GZR/EBR ± RBV: (1) treatment-naive
patients (TN; N=801), and (2) patients who previously failed
peginterferon + RBV ± first-generation protease inhibitor (TE;
N=607). Demographic factors and presence of resistance-associated
variants (RAVs) that were fit (ie, >25% of the overall
baseline viral load) were considered. Univariate logistic regression
models were fitted one variable at a time in assessing
the potential association with SVR12. Multivariable logistic
regression (MVLR) models with forward selection were then
applied to identify significant (ie, P < 0.1) independent predictors
of SVR12. Results: In the MVLR, among TN patients, age,
sex, cirrhosis, HIV coinfection, baseline NS3 RAVs, and use
of RBV did not impact SVR12 rates. Among TN GT1a-infected
patients, baseline HCV RNA level and baseline NS5A RAVs
conferring >5-fold shift in the potency of EBR in vitro (termed
NS5A >5× RAVs) were identified as significant predictors
of SVR12. Baseline HCV RNA had a significant impact only
when NS5A >5× RAVs were present, representing 5.3% of
the GT1a population. No significant predictors were identified
among GT1b-infected patients. Among TE patients, no significant
predictors were identified for GT1b-infected patients or
in GT1a-infected patients with prior relapse. Among GT1a-infected
patients with prior on-treatment failure, female patients
and noncirrhotics had higher SVR12 rates, and the addition of
RBV and/or longer treatment durations had a positive impact
on SVR12. The most prevalent (>1%) NS5A >5× RAVs in both
TN and TE patients were L31M and Y93H. Baseline NS5A >5×
RAVs, which were detected in 8% of TE GT1a-infected patients
had a significant negative impact on SVR12; this impact was
confined to the 12-wk treatment duration, as no patient treated
for 16 or 18 weeks with RBV experienced virologic failure.
Conclusion: GZR/EBR ± RBV is highly effective among GT1-infected
patients. Among GT1a-infected patients, presence of fit
NS5A >5× RAVs at baseline impacts efficacy. These RAVs are
uncommon (