A Prospective Italian Study on Baseline NS3 and NS5A Resistance to Direct-Acting Antivirals in a Real-World Setting of HIV-1/HCV Coinfected Patients and Association with Treatment Outcome.

We prospectively evaluated the frequency of natural resistance-associated substitutions (RASs) in the NS3 and NS5A regions according to different HCV genotypes and their possible effect on treatment outcome in HIV-1/HCV patients treated with direct-acting antivirals (DAAs). Baseline RASs in the NS3 and NS5A domains were investigated in 62 HIV-1/HCV patients treated with DAAs: 23 patients harbored HCV-GT1a, 26 harbored GT3a, and 13 harbored GT4d. A higher occurrence of RASs was found in the NS3 domain within GT1a (13/23) than GT3a (0/26) or GT4d (2/13). With regard to treatment outcome, NS3 RASs were detected in 14/56 patients with sustained virological response (SVR) and in 1/6 non-responder (NR) patients. Occurrence of RASs of NS5A domain was lower in SVR (4/56, had RASs) than in NR (3/6, had RASs). Evaluation of RASs at baseline instead of at virological failure, especially in the NS5A domain, could positively influence the choice of new DAA combinations for the treatment of HIV-1/HCV patients.