Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 206
*Purpose: Two recent pilot trials have shown that transplanting hepatitis C (HCV) viremic kidneys in to HCV negative recipients is feasible. These trials used 12 weeks of direct-acting anti-viral (DAA) therapy to treat donor-derived HCV viremia. We conducted an open-label single-center nonrandomized trial (ClinicalTrials.gov: NCT03249194) in two phases to determine the feasibility of using ultra short-term DAA prophylaxis before and after kidney transplantation from deceased HCV-infected viremic donors to non-HCV-infected recipients (D+/R- transplants).
*Methods: Waitlisted HCV negative kidney transplant candidates with expected wait time of >2 years, with age>60 years, or any age with at least two co-morbidities (diabetes, heart disease, peripheral vascular disease or stroke) without significant liver fibrosis assessed by transient elastography were enrolled. After administration of short course (2-4 days) prophylactic Sofusbuvir/Velpatasvir (SOF/VEL), patients were screened for HCV RNA at Days 3, 7, 14, 21, 28, 42, Months 3, 6 and 12. Development of viremia triggered a full 12 week course of DAA therapy.
*Results: Overall, 25 patients (mean age=60 years; 36% females; 60% African-American) received D+/R- transplants. The mean wait time to transplant from enrollment was 28 days and the mean donor KDPI was 59%. The median donor viral load was 5.6E+05 IU/mL (IQR:1.08E+03-1.98E+07) although 5 samples could not be analyzed possibly due to degradation. 67% were Genotype (GT) 1a, 22% were GT 3 and 11% were GT 2. At a median follow-up of 4.6 months (IQR: 1.8-15months) post-transplant, both patient and graft survivals were 100%. Average kidney function as measured by eGFR was 57±16mL/min/1.73m2. There were two episodes (8%) of acute T-cell mediated rejection that were reversed with therapy. There were no cases of liver dysfunction. In Phase I, ten D+/R- recipients 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 GT1a). Of these 3, two patients achieved sustained virologic response with a subsequent course of DAA while one patient (with NS3/4A and NS5A resistance mutations) did not. In Phase II, 15 D+/R- patients received two additional doses of SOF/VEL on Days 2 and 3 post-transplant. Viral transmission rate decreased to 13%, with only two patients acquiring HCV (one GT2 and one GT3). Both patients have undetectable viral loads after initiating 12 weeks of DAA therapy.
*Conclusions: Our data suggests that ultra-short duration DAA prophylaxis was largely effective in preventing donor-derived HCV transmission and has the potential of resulting in significant cost-savings by avoiding DAA therapy in a large majority of D+/R- transplants.
To cite this abstract in AMA style:Gupta G, Yakubu I, Bhati C, Ferreira-Gonzalez A, Kumar D, Moinuddin I, Kamal L, King A, Levy M, Sharma A, Coterell A, Reichman T, Khan A, Kimball P, Stiltner R, Baldecchi M, Brigle N, Gehr T, Sterling R. Ultra-Short Duration Direct Acting Anti-Viral Prophylaxis to Prevent Virus Transmission from Hepatitis C Viremic Donors to Hepatitis C Negative Kidney Transplant Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/ultra-short-duration-direct-acting-anti-viral-prophylaxis-to-prevent-virus-transmission-from-hepatitis-c-viremic-donors-to-hepatitis-c-negative-kidney-transplant-recipients/. Accessed June 26, 2019.
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