Short Perioperative Antiviral Prophylaxis for Hepatitis C Viremic Donor Kidney Transplantation: Outcomes in 204 Recipients

Background. Kidney transplantation using hepatitis C virus (HCV) nucleic acid test–positive donors for HCV-negative recipients (D + /R − ) has expanded in the direct-acting antiviral (DAA) era, but real-world outcomes with short-course prophylaxis remain limited. We report the largest cohort to date managed with a 7-d perioperative prophylactic DAA strategy. Methods. Single-center prospective observational study of 204 consecutive HCV nucleic acid test–positive donor to HCV-negative recipient kidney transplants performed between December 2018 and August 2025. All recipients received sofosbuvir/velpatasvir 400 of 100 mg daily for 7 d beginning on the day of transplantation. HCV RNA was monitored through 90 d posttransplant. Breakthrough viremia triggered full-course DAA therapy. Results. Donor-derived breakthrough viremia occurred in 15 of 204 recipients (7.4%; 95% confidence interval, 4.2%-11.9%). Most cases (93.3%) were detected by postoperative day 28. Nonstructural protein 5A resistance-associated substitutions were identified in 4 of 8 tested breakthrough cases. First-line retreatment achieved sustained virologic response (SVR) at 12 wk in 14 of 15 (93.3%); 1 patient required salvage therapy, yielding overall SVR at 12 wk of 15 of 15 (100%), although 93% required insurance prior authorization (median delay 36 d). One-year patient and graft survival were 96.6% and 94.1%, respectively, with stable graft function through 12 mo (mean estimated glomerular filtration rate 53.0 ± 22.0 mL/min/1.73 m 2 ). Conclusions. Seven-day perioperative sofosbuvir/velpatasvir prophylaxis achieved SVR after prophylaxis alone in >92% of D + /R − kidney transplant recipients, with favorable 1-y clinical outcomes. Given the nonstructural protein 5A resistance-associated substitutions observed, we have transitioned to 7-d glecaprevir/pibrentasvir prophylaxis; outcomes will be reported via the REFORM-HEPC registry. These findings provide real-world evidence supporting the feasibility of short-course antiviral prophylaxis in HCV-viremic donor kidney transplantation.