Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection.

Abstract

BACKGROUND AND AIMS

Shortened duration therapy for acute and recent hepatitis C virus (HCV) infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens, however large randomised studies are lacking.

METHODS

REACT was an NIH-funded multicentre international, open-label, randomised, phase 4 non-inferiority trial examining the efficacy of short course (6 weeks) versus standard course (12 weeks) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection <= 12 months). Randomisation occurred at week 6. The primary endpoint was SVR12 in the intention-to treat (ITT) population. A total of 250 participants were planned for enrolment. On advice of the data safety and monitoring board the study was halted early.

RESULTS

Primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n=93), standard arm (n=95). Ninety seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI: -18.6, 1.0). By modified ITT analysis in which non-virological reasons for failure were excluded (death, reinfection, lost to follow-up) SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p=0.025).

CONCLUSIONS

In this randomised study in recent HCV infection, 6 weeks sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12 weeks duration.

LAY SUMMARY

In this randomised trial one hundred and eighty people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were nine cases of relapse after treatment in the short course and two using the standard course. A shortened course of 6 weeks therapy for hepatitis C infection was considered not as effective as a standard twelve week course in people with recently acquired hepatitis C infection.

TRIAL REGISTRATION

Clinicaltrials.gov Identifier: NCT02625909.