Effectiveness and Safety of Sofosbuvir/Velpatasvir/ Voxilaprevir in Patients with Chronic Hepatitis C Previously Treated with DAAs

Abstract Background Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. Methods Prospective multicentre study including previously DAA-treated patients who were retreated with SOF/VEL/VOX. The primary endpoint was SVR12. Data on safety and tolerability were also recorded. Results 137 patients included: 75% men, 35% with liver cirrhosis. Most were infected by HCV genotype (GT) 1 or 3. Most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p=0.05) and those with GT3 infection (80%, p Conclusion Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of RASs. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group.