Direct acting antivirals for the treatment of elderly patients with HCV advanced disease in the real life practice

Results: 28/41 patients were relapser, after a median (IQR) of 4.6 (4.2-13.7) weeks post-end of treatment; other 11 patients had a virological-breakthrough at a median (IQR) of 14 (1219) weeks; 2 were non-responders. 17/28 relapsers (61%) had received sofosbuvir + ribavirin for 24 weeks, and 7 sofosbuvir + simeprevir± ribavirin for 12 weeks. Generally, ribavirin use was significantly more frequent in relapsers than in breakthrough/non-responders (86% vs 54%, p=0.049). Overall, 25/41 patients (61%) showed at least one RAV at failure. 17/41 (41%) patients showed major RAVs on ≥2 DAAtargets, including 10/10 treated with NS3+NS5a combinations. RAVs prevalence was significantly higher in breakthrough/nonresponders than in relapsers (100% vs 48%, pu003c0.001), and in patients who did not receive ribavirin (100% vs. 48%, p=0.003). All 13 NS5A-failing patients showed NS5A RAVs at failure, vs 17/18 PIfailures in NS3 (including 7/8 sofosbuvir + simeprevir± ribavirin) and 10/33 NS5B-failures in NS5B (pu003c0.001). Notably, 2 breakthrough-patients showed the sofosbuvir-RAV S282T (1 GT3a treated with sofosbuvir alone, 1 GT4a with sofosbuvir + simeprevir), while 6 relapsers to sofosbuvir + ribavirin or sofosbuvir + simeprevir± ribavirin showed the resistance-pattern L159F+C316N (all GT1b). Major RAVs were detected at baseline in 3/16 patients with available test (GT1b: NS3D168V+NS5AY93H; GT1a: NS3V55A; GT4d: NS3D168E+NS5AR30S) and were confirmed at failure, always in association with additional new RAVs. The putative sofosbuvir resistance-pattern L159F+C316N was found in 2 patients at baseline, and confirmed at sofosbuvir-failure without additional RAVs. Conclusions: The high prevalence at failure of major RAVs in almost half of cases involving 2 DAAs-targets advocates for unconventional, resistance-based regimens, for appropriate retreatment.