An early 6-month analysis of the DONATE HCV Trial demonstrated that hearts and lungs can be safely transplanted from HCV-infected donors using a shortened, 4-week, pre-emptive course of direct acting antivirals (DAA). Whether early findings are sustained in the longer-term remain an important area of investigation.
DONATE HCV is a single-center trial to transplant thoracic organs from HCV viremic donors, irrespective of HCV genotype, to HCV-uninfected adults. Sofosbuvir/velpatasvir, a pan-genotypic DAA, was administered for 4 weeks, beginning within hours of transplant. The primary composite outcome of HCV clearance and graft survival at 6 months post-transplant are now extended to the longer-term at 1- and 3-years. We also report on grade 3 or higher adverse events (AEs). (NCT03086044)
Between March 2017 and December 2019, 65 participants were enrolled: 53 received lung and 12 received heart transplants. The median donor HCV viral load (VL) was 742,000 IU/mL (IQR 127,000 - 4.69 million). 56 of 65 (86%) recipients had detectable HCV VL immediately after transplant, with median VL of 2,000 IU/mL (IQR 800 - 9,000). HCV VL became negative by 2 weeks and subsequently remained undetectable in all participants. 63 of 65 (97%), 60 of 63 (95%), 46 of 51 (90%), and 19 of 24 (79%) participants were alive with excellent graft function and an undetectable HCV VL at 6 months, 1-year, 2-years, and 3-years post-transplant, respectively. 22 of 65 (34%) and 28 of 63 (44%) had acute cellular rejection requiring treatment at 6 months and 1-year post-transplant, respectively. 3 of 65 (5%) and 3 of 63 (5%) had antibody mediated rejection at 6 months and 1-year post transplant, respectively. No treatment-related AEs were identified. Outcomes between transplant recipients from HCV donors vs. non-HCV donors were similar, including the occurrence of renal failure, respiratory failure, and non-HCV infections.
These data demonstrate that recipients of thoracic organs transplanted from HCV viremic donors who receive a shortened antiviral treatment course initiated within hours of transplant, have excellent longer-term graft and recipient survival with similar AE profiles compared to transplant recipients who received thoracic organs from non-HCV donors.