Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., D.M.B., M.A.C., G.M., N.B., R.W., A.R., F.F.N., D.O., D.L.S., M.S., N.M.D.).
Johns Hopkins University School of Medicine and Johns Hopkins University, Baltimore, Maryland (J.S.).
Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource.
To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation).
Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649).
10 HCV D+/R- kidney transplant candidates older than 50 years with no available living donors.
Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy.
The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis.
Among 10 HCV D+/R- transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.
Nonrandomized study design and a small number of patients.
Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.
PRIMARY FUNDING SOURCE:
Merck Sharp & Dohme Corp.