Direct-Acting Antiviral Treatment Failure and Retreatment Strategies Following Hepatitis C-Positive Solid Organ...

Transplanting solid organs from hepatitis C virus (HCV) nucleic acid testing (NAT+) donors (D+) into HCV-negative recipients (R-) has become more common with the development of curative direct-acting antiviral (DAA) treatment. Limited information exists to guide retreatment strategies for patients not achieving sustained virologic response (SVR) with DAAs. This multisite case series examines retreatment strategies and subsequent SVR rates in HCV-negative solid-organ transplant (SOT) recipients who did not achieve SVR following reactive initial DAA therapy following NAT+ SOT.

A retrospective multisite case series was conducted on patients not achieving SVR with initial DAA treatment post-NAT+ HCV SOT between September 2016 and September 2022 across four tertiary medical centers in the United States.

Thirteen patients were identified, predominantly receiving HCV NAT+ kidneys (77%) and SOF/VEL for 12 weeks as initial DAA therapy (43%). Baseline resistance testing was not performed. Median time to treatment initiation post-SOT was 35 [IQR 22-41] days, and to retreatment postpositive viral load was 35 days [IQR 17-76]. Most patients (62%) were retreated with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks. Two patients required retreatment extension with SOF/VEL/VOX and SOF/VEL/VOX + ribavirin (RBV) from 12 to 24 weeks due to persistent viremia. Only one patient did not achieve SVR following retreatment with SOF/VEL/VOX for 12 weeks but did achieve SVR after a third course of treatment with SOF + GLE/PIB + RBV for 24 weeks.

Despite initial DAA failures, all HCV-negative SOT recipients achieved SVR following one or more courses of retreatment with DAAs.