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

Ann Intern Med. 2018 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amides
  • Antiviral Agents / therapeutic use*
  • Benzofurans / therapeutic use
  • Carbamates
  • Cyclopropanes
  • Drug Therapy, Combination
  • Feasibility Studies
  • Female
  • Genotype
  • Graft Rejection
  • Graft Survival
  • Hepatitis C / drug therapy*
  • Hepatitis C / transmission*
  • Humans
  • Imidazoles / therapeutic use
  • Kidney / virology*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Quinoxalines / therapeutic use
  • RNA, Viral / analysis
  • Sofosbuvir / therapeutic use
  • Sulfonamides
  • Tissue Donors*
  • Treatment Outcome

Substances

  • 2-(pyrrolidin-2-yl)-5-(2-(4-(5-(pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole
  • Amides
  • Antiviral Agents
  • Benzofurans
  • Carbamates
  • Cyclopropanes
  • Imidazoles
  • Quinoxalines
  • RNA, Viral
  • Sulfonamides
  • grazoprevir
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02781649