Adherence and sustained virologic response in HCV treatment: A real-world comparison of major pangenotypic direct-acting antivirals

Pangenotypic direct-acting antivirals (DAAs) have transformed the management of hepatitis C virus (HCV) infection, enabling high sustained virologic response (SVR) rates across diverse patient populations. Real-world data comparing adherence and treatment outcomes between commonly used pangenotypic regimens remains limited. We compared adherence and SVR outcomes between sofosbuvir/velpatasvir (SOF/VEL; Epclusa) and glecaprevir/pibrentasvir (GLE/PIB; Maviret) across clinically relevant HCV subpopulations. We conducted a retrospective cohort study using Leumit Health Services data, including 740 adults treated with SOF/VEL ( n = 395) or GLE/PIB ( n = 345) between 2019 and 2023. Demographic and clinical characteristics were extracted. Adherence was defined as receipt of ≥80% of prescribed doses. SVR rates were evaluated overall and across clinically relevant subgroups. Multivariable logistic regression identified independent predictors of reduced adherence and SVR. SVR rates were high and comparable between SOF/VEL and GLE/PIB (95.7% vs 95.4%, p = 0.92), including among patients with advanced fibrosis or cirrhosis. High adherence was observed in 83.0% of SOF/VEL-treated and 86.1% of GLE/PIB-treated patients and was strongly associated with SVR (97.1% vs 87.0% among those with lower adherence, p < 0.01). Lower adherence and SVR rates were observed among people who inject drugs and individuals with alcohol use disorder. In multivariable analyses, intravenous drug use, excessive alcohol consumption, and polypharmacy independently predicted reduced adherence, whereas treatment regimen did not. SOF/VEL and GLE/PIB demonstrate similarly high effectiveness in routine clinical practice. Adherence is the principal determinant of treatment success, particularly in high-risk populations. Targeted strategies to support adherence are essential to optimizing real-world HCV treatment outcomes.