Efficacy of direct-acting antiviral regimens for acute HCV infection: a systematic review and meta-analysis

Abstract Background Acute and recently acquired hepatitis C virus (HCV) infection clusters in men who have sex with men living with HIV and in people who inject drugs, where early cure benefits both the individual and transmission control. The best interferon-free dual direct-acting antiviral (DAA) regimen and treatment duration, including short courses, remain undefined. Methods MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched to 1 July 2026 for studies of interferon-free dual-DAA therapy in acute or recently acquired HCV reporting SVR12. Each study was appraised as a single-arm case series, and proportions were pooled by random-intercept logistic regression. Pre-specified subgroups were regimen, treatment duration, study design, and HIV status. Results Fourteen studies (19 single-arm analysis units; 1078 treated patients) were included. Pooled SVR12 was 97.7% (95% CI 94.7–99.1; 1043/1078; I² = 30.4%). SVR12 rates increased with treatment duration, from 84.8% (74.1–91.6) at 4 weeks and 91.7% (86.2–95.1) at 6 weeks to 99.4% (97.5–99.9) at 8 weeks and 97.4% (91.7–99.2) at 12 weeks (between-subgroup p < 0.001), whereas it did not differ by regimen ( p = 0.608), study design ( p = 0.764), or HIV status ( p = 0.975). The pooled estimate was stable across sensitivity analyses (trials only, exclusion of the high-risk study, and leave-one-out). Conclusion Dual-DAA therapy was associated with a high pooled SVR12 in acute and recently acquired HCV, with cure differing by treatment duration. These findings support early treatment and favour a course of at least eight weeks. Given the predominantly single-arm evidence and the partial confounding of regimen with duration, randomised duration-comparison trials are needed to confirm the optimal short-course strategy.