NS 5 A treatment-naive patients : findings from two randomized trials

Background & Aims: We report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virologic response (SVR) with prior SOFbased, non-NS5A inhibitor-containing regimens. Methods: The RESCUE study enrolled HCV mono-infected adults with genotype 1 or 4. Non-cirrhotic participants were randomized to 12 weeks of LDV/SOF or LDV/SOF+RBV. Compensated cirrhotic participants were randomized to LDV/SOF+RBV (12 weeks) or LDV/SOF (24 weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF+RBV (12 weeks) or LDV/SOF (24 weeks). Both studies used SVR at 12 weeks post-treatment (SVR12) as the primary endpoint. Results: In the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF+RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF+RBV for 12 weeks or LDV/SOF for 24 weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, 7 participants were randomized (cirrhotic n=1; GT1a n=5) and all attained SVR12, with no serious AEs or premature discontinuations. Conclusions: In this SOF-experienced NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved.