Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial

Abstract

Background: 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.

Objective: 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).

Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649).

Setting: Single center.

Participants: 10 HCV D+/R- kidney transplant candidates older than 50 years with no available living donors.

Intervention: 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.

Measurements: 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.

Results: 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.

Limitation: Nonrandomized study design and a small number of patients.

Conclusion: 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.

Conflict of interest statement

Disclosure of Conflicts of Interest

C. Durand has received research grants from Bristol Meyers Squibb, Gilead Sciences Merck Pharmaceuticals, and Viiv Healthcare, and has served as a scientific advisor for Bristol Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals. J. Sugarman serves on Merck KGaA’s Bioethics Advisory Panel and Stem Cell Research Oversight Committee; and Quintile’s Ethics Advisory Panel. M. Sulkowski served as scientific advisor for AbbVie, Gilead Sciences, Cocrystal, Janssen, Merck Pharmaceuticals, Trek and also received research grants from AbbVie, Gilead Sciences, and Merck Pharmaceuticals. N. Desai has served as a scientific advisor for Merck Pharmaceuticals.

Figures

Figure 1. Pre- and Post-transplant HCV RNA Among HCV-uninfected Recipients of HCV+ Donor KT

HCV plasma RNA log10 IU/mL pre-transplant, during DAA treatment on post-operative day 1, post transplant weeks 1, 2, 4, 8 and 12 and after DAA treatment on follow-up weeks 4, 8, and 12. Lower limit of quantification is 15 IU/mL.

Figure 2. Post-transplant Liver Function Tests Among HCV-uninfected Recipients of HCV+ Donor KT

(A) ALT values and (B) AST values measured at baseline and during post-transplant follow up. *Missing for one patient

Figure 3. Pre- and Post-Transplant HCV-specific CD8+ T cell Responses among Among HCV-uninfected Recipients of HCV+ Donor KT

The number of positive peptide pools identified for each recipient pre-transplant and at follow-up week 8 post-transplant are shown. T cell responses were measured by IFN-γ ELISpot using a matrix of 6 peptide pools containing overlapping peptides of optimal cytotoxic T lymphocyte HCV epitopes. Pools with > 50 spot forming cells/million PBMC were considered positive.