8-week glecaprevir/pibrentasvir shows 96.2% SVR12 in acute HCV treatment-naïve adultsCan a short treatment course cure most cases of acute hepatitis C?

BACKGROUND & AIMS: With over 1 million new HCV infections in 2022, treating acute HCV is essential to achieve WHO's HCV elimination goal. Although guidelines recommend prompt treatment, no direct-acting antiviral is approved for acute HCV outside of the US, leading to loss of patients to care while waiting for chronicity, and increased onward transmission. This single-arm, phase IIIb study evaluated the efficacy and safety of an 8-week glecaprevir/pibrentasvir regimen in treatment-naïve adults with acute HCV. METHODS: Analyzed populations included intention-to-treat (ITT; all patients receiving ≥1 glecaprevir/pibrentasvir dose) and modified ITT, which excluded non-virologic failures (mITT-VF). The primary and key secondary efficacy endpoints were achievement of sustained virologic response at post-treatment Week 12 (SVR12) in the ITT and mITT-VF populations. Secondary endpoints included on-treatment virologic failure, post-treatment relapse, and reinfection in the ITT population. Treatment-emergent adverse events (TEAEs) and safety laboratory values were assessed. RESULTS: Overall, 286 adults were enrolled and treated; 14.3% were recent/current users of injection drugs, 49.7% were HCV/HIV coinfected, and 64.2% had HCV genotype 1. SVR12 was achieved by 96.2% (95% CI 93.2%-97.8%) in the ITT population (n = 286), and 100% in the mITT-VF population (n = 275). No TEAEs of hepatic decompensation/failure occurred; 1 (0.3%) patient discontinued due to a non-treatment-related TEAE; 3.5% of patients experienced serious TEAEs, none treatment-related; no deaths occurred. No patient with baseline alanine aminotransferase elevations of Grade 1-3 worsened to a higher grade during treatment, and all patients with baseline Grade 2-4 improved to a lower grade at the final treatment visit. CONCLUSIONS: An 8-week glecaprevir/pibrentasvir regimen was efficacious and well-tolerated in patients with acute HCV. These results support glecaprevir/pibrentasvir use in HCV test-and-treat models, potentially streamlining the care cascade, reducing transmission, and supporting HCV elimination. IMPACT AND IMPLICATIONS: Currently, approved hepatitis C treatments are available only for chronic HCV in most geographies, with glecaprevir/pibrentasvir recently approved in the US for acute HCV. The lack of therapeutic options delays treatment initiation, increasing the risk of disengagement among people who inject drugs and other vulnerable groups, and contributing to onward transmission. This study demonstrates that 8-week glecaprevir/pibrentasvir therapy is efficacious and safe in patients with acute HCV infection, supporting its role as a recently approved treatment for acute HCV. Availability of an approved treatment for acute HCV will support the implementation of test-and-treat strategies in outreach settings for key prevalent populations, reducing delays and improving care retention, particularly among high-risk individuals. CLINICAL TRIAL NUMBER: NCT04903626.