Purpose / DescriptionThe ASTRAL-3 trial was published in tandem with the similar trial involving patients with genotype 2 infection (ASTRAL-2). In this randomized, open-label phase 3 trial, investigators compared the efficacy of the fixed-dose combination of sofosbuvir-velpatasvir for 12 weeks with sofosbuvir plus ribavirin for 24 weeks in patients with genotype 3 HCV infection. Of the 552 patients enrolled in the study, 30% had compensated cirrhosis and 26% were treatment-experienced. The overall SVR12 rate was 95% in the sofosbuvir-velpatasvir arm and 80% in the sofosbuvir plus ribavirin arm (P-value<0.001). Among those patients with cirrhosis who received sofosbuvir-velpatasvir, the SVR12 rate were 93% for treatment-naïve and 89% for treatment-experienced patients. Among the 274 patients screened for baseline NS5A resistance-associated variants, the SVR12 rate was 88% for the 43 patients who had variants compared with 97% among those who did not.The investigators concluded the 12-week regimen of sofosbuvir-velpatasvir regimen was superior to the standard 24-week regimen of sofosbuvir plus ribavirin in patients with chronic HCV genotype 3 infection. The most substantial differences occurred in treatment experienced patients with those with cirrhosis.