by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
June 1, 2021
Matthews GV, Bhagani S, Van der Valk M, et al, REACT study group; Protocol Steering Committee. Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection. J Hepatol. 2021 May 20; S0168-8278(21)00336-6. doi: 10.1016/j.jhep.2021.04.056. PMID: 34023350.
This open-label international phase 3 trial aimed to determine whether six weeks of sofosbuvir/velpatasvir is non-inferior to twelve weeks of sofosbuvir/velpatasvir among people with recent hepatitis C (HCV) infection. People with HCV-HIV coinfection were eligible for inclusion, and participants with coinfection represented 69% of the final population analyzed. Recruitment was halted mid-2019 given interim DSMB concerns regarding six-week arm efficacy: the final population for primary analysis thus consisted of 188 participants (93 in the six-week [short] arm and 95 in the twelve-week [standard] arm). Overall, study adherence was good and noted to be higher in the short arm. Twenty-three percent of participants experienced a treatment-related adverse event (no difference by arm), with the vast majority as Grade 1-2 events. Intent-to-treat analysis demonstrated an end-of-treatment response of 91.4% in the short vs. 91.6% in the standard arm, and SVR12 of 81.7% in the short vs. 90.5% in the standard arm. Criteria for non-inferiority (selected threshold: 12%) was not met. Suboptimal efficacy in the short arm was driven primarily by higher post-treatment relapse, observed in 10% of participants in the short vs. 2% in the standard arm. Generation of resistance associated substitutions was limited and almost all participants with relapse were subsequently retreated successfully.
Although investigators observed higher relapse rates in participants receiving short-course sofosbuvir/velpatasvir for recent HCV infection, these findings add to emerging evidence suggesting that early treatment is safe, feasible, and fairly effective for acute HCV. Treatment guidelines currently incorporate a “test and treat” strategy which includes a recommendation that patients with acute HCV infection should no longer be monitored for possible spontaneous resolution, but rather treated upon initial diagnosis. However, there are no distinct recommended regimens for acute HCV at this time (i.e. the same regimens used for chronic infection are recommended for acute infection). Given the not infrequent “real world” experience of treatment interruptions or abbreviated treatment courses as well as ongoing hepatitis elimination efforts, highly effective short-course treatment options remain highly desirable and a key area for research and implementation.
The author has no conflicts of interest to disclose.
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