Shortened duration therapy for acute and recently acquired HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral agents (DAAs), however guidelines remain conservative in their recommendations with no currently approved regimens for this indication.
The REACT study was an NIH-funded multicentre international, open-label, randomised, phase 4 non-inferiority trial examining the efficacy of short course (6 weeks, Arm A) versus standard course (12 weeks, Arm B) therapy with sofosbuvir/velpatasvir for recently acquired HCV infection (estimated duration of infection <= 12 months). Randomisation was at week 6 and stratified by site and HIV status. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12) reported in the intention-to treat (ITT) population. A total of 250 participants were planned for enrolment and DSMB analysis was scheduled after the first 50 participants in each arm reached SVR12. Following the initial DSMB review, a second review was scheduled following 60 participants through SVR12 in each arm.
At second DSMB review, 185 participants were enrolled, 165 had been randomised and 127 were through SVR12; n=65 in Arm A and n=60 in Arm B. Of those randomised, 98% were male, and 72% HIV positive. The predominant genotype was 1 (65%) and median baseline viral load 5.6 log10IU/ml. 38% were reinfections. At second review (May 2019), the DSMB recommended study cessation for evidence of inferiority in the short arm (A). By ITT SVR12 was 78% (53/65) in Arm A (95%CI 70-90) versus 95% (57/60) in Arm B (95%CI 86-99) (p=0.021). Relapse occurred in 6/65 participants in Arm A (9%, 95%CI 3-19) versus 0 in Arm B (95% CI 0-6). Median baseline viral load in people with viral relapse was 6.4log10IU/ml (range 5.9-7.1 log10IU/ml). Two further participants in Arm A had virological failure at end of treatment, one had reinfection, two died, and four lost to follow-up. Three participants in Arm B were lost to follow-up.
In this randomised study of treatment for recently acquired HCV infection, 6 weeks sofosbuvir/velpatasvir was inferior to 12 weeks. Final analysis of the full randomised dataset will be completed October 2019.