01 Ago HCV retreatment efficacy after 1st line failure is decreased by NS5A resistance, short regimens and lack of ribavirin: how “easy” can we go in real-life?

Background: Retreatment of HCV-patients who fail to achieve a sustained viral response (SVR) is currently a major challenge. Whereas international guidelines recommend drug-class switch or “unconventional” drug-associations, we analyzed the real-life efficacy of HCV-retreatment, and the usefulness of baseline (BL) genotypic resistance testing (GRT).
Main Results: Within the collaborative network VIRONET-C, 100 patients were retreated after NS5A-inhibitors (NS5Ai)±ribavirin (RBV, N=14); simeprevir (SIM)+sofosbuvir (SOF)±RBV (N=23); or SOF+RBV (N=63) failure.
Ad interim SVR12 rate was 80.4% (74/92), but it was reduced to 50.0% (7/14) in patients retreated not according guidelines nor BL-GRT, vs. 87.5% (49/56) achieved by following guidelines (46/56 with also BL NS5A-GRT), and 81.8% (18/22) by following viral resistance profile (p<0.01).
In the 85 patients retreated with NS5Ai, SVR12 was reduced by short RBV-free regimens (25.0% [2/8] 12wk noRBV vs 85.7% [6/7] of 12wk+RBV, 100% [11/11] of 24wk noRBV, and 83.1% [49/59] of 24wk+RBV; p<0.01), by prior NS5Ai-experience (40.0% [2/5] vs 82.5% [66/80] in NS5A-naïve; p=0.05), and by BL NS5A-RASs (50% [8/16] vs 85.5% [47/55] in patients without; p=0.01).
After 2nd line failure, 8/12 patients tested showed multiple and/or multiclass RASs.
Conclusions: Integration of BL-GRT in retreatment personalization may help to optimize efficacy and to identify patients with complex resistance that are natural candidates for future generation regimens.