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

• Published in: Journal of hepatology Vol. 75; no. 4; pp. 829 - 839
• Main Authors: Matthews, Gail V., Bhagani, Sanjay, Van der Valk, Marc, Rockstroh, Juergen, Feld, Jordan J., Rauch, Andri, Thurnheer, Christine, Bruneau, Julie, Kim, Arthur, Hellard, Margaret, Shaw, David, Gane, Ed, Nelson, Mark, Ingiliz, Patrick, Applegate, Tanya L., Grebely, Jason, Marks, Phillipa, Martinello, Marianne, Petoumenos, Kathy, Dore, Gregory J., van der Valk, Marc, Dore, Greg, Marks, Pip, Matthews, Gail, Applegate, Tanya, Feld, Jordan, Rockstroh, Jürgen, Amjad, Sophia, Tu, Elise, Tamaddoni, Mahshid, Thurnheer, Maria Christine, Gilleece, Yvonne, Fraser, Chris, Moriggia, Alberto, Lutz, Thomas, Moon, Juhi, Read, Phillip, Kim, Arthur Y., Ustianowski, Andrew, Cordes, Christiane, Sasadeusz, Joe, Hull, Mark, Braun, Dominique
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2021; Elsevier Science Ltd
• Subjects: acute; Adult; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Australia; Canada; Carbamates - pharmacology; Carbamates - therapeutic use; direct-acting antivirals; Drug Combinations; Female; Germany; HCV; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C - physiopathology; Heterocyclic Compounds, 4 or More Rings - pharmacology; Heterocyclic Compounds, 4 or More Rings - therapeutic use; HIV; Human immunodeficiency virus; Humans; Infections; Interferon; Male; Middle Aged; Netherlands; New Zealand; recently acquired; short duration; Sofosbuvir - pharmacology; Sofosbuvir - therapeutic use; Switzerland; Time Factors; treatment; Treatment Outcome; United Kingdom; New Zealand; Canada; Netherlands; United Kingdom; Australia; Switzerland; Germany; treatment; acute; HCV; short duration; direct-acting antivirals; recently acquired
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2021.04.056

Shortened duration therapy for acute and recent 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. REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. The 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 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss 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). In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. In this randomised trial, 188 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 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. NCT02625909. [Display omitted] •REACT is a randomised study of short course DAA therapy for recently acquired HCV.•188 participants were treated with either 6 or 12 weeks sofosbuvir/velapatasvir.•The study population was predominantly cis-male and included a high proportion living with HIV.•The study was stopped early due to the high rate of virological relapse in the short course arm.•Six weeks of sofosbuvir/velapatasvir cannot be considered non-inferior to 12 weeks.