*Purpose: Previous trials in kidney transplantation (KT) have described a 12-week course of direct-acting anti-viral drugs (DAA) to treat HCV transmission from infected donors to HCV negative recipients (D+/R- KT). The cost and access to DAAs remain a major barrier though and delayed therapy has been associated with de-novo donor-specific antibody formation and fibrosing cholestatic hepatitis. Thus, a prophylactic and short-course strategy may be safer and more cost-effective. We recently reported that an ultra-short duration (2-4 days peri-operative) DAA prophylaxis using pangenotypic sofosbuvir/velpatasvir (SOF/VEL) in D+/R- KT was able to prevent HCV transmission in a majority (88%) but not all, KT. Thus, the minimal duration of DAA prophylaxis remains unknown. We report our cumulative experience of D+/R- KT based upon an adaptive iterative trial design where prophylaxis was extended to 7 days.

*Methods: Active wait listed patients (pts) were eligible if they met the following criteria: absence of living donor; panel reactive antibody≤50%; ≤1 previous KT; and absence of significant chronic liver disease. The primary outcome was HCV transmission to recipient, defined as two consecutive + HCV RNA tested at Day 7 and 14 post-KT. All pts received standard of care induction rabbit anti-thymocyte globulin followed by triple immunosuppression with tacrolimus, mycophenolate and prednisone. After a single adult KT, pts were screened for HCV RNA at periodic intervals. Confirmed HCV transmission triggered 12-weeks of DAA therapy.

*Results: Of a total of 163 enrolled, 80 pts (mean age 57 yrs; 32% females; 55% African-American) received D+/R- KT from 11/17 to 10/19. The mean wait time enrollment to KT was 34 days and the mean donor KDPI was 56%. At a median follow-up of 8 months (IQR: 1-23months) post-KT, death-censored graft survival was 99% and pt survival was 98%. There were no cases of liver dysfunction or other HCV associated complications. In Group 1, 10 pts received one dose of pangenotypic SOF/VEL immediately pre-transplant and then one dose on post-transplant day 1. Viral transmission rate was 30% [3/10; All Genotype (GT)1]. Of these 3, one pt was a non-responder to subsequent full course DAA therapy possibly secondary to non-adherence. In Group 2, 42 pts received two additional doses of SOF/VEL on days 2 and 3 post-KT. Viral transmission rate decreased to 9.5% (4/42; 1 GT1, 1 GT2, 2 GT3). All achieved sustained virologic response with subsequent DAA therapy. In Group 3 (N=28), prophylaxis was extended to 7 days (Days 0-6 of KT) with one case (3.5%) of donor-derived HCV transmission till most recent follow-up.

*Conclusions: Our data suggests that 7-day DAA prophylaxis is effective in preventing donor-derived HCV transmission and could result in significant cost-savings and increase access to these transplants all over the world.

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