Monitoring of Cytomegalovirus (CMV)-Specific Cell-Mediated Immunity in Heart Transplant Recipients: Clinical Utility of the QuantiFERON-CMV Assay for Management of Posttransplant CMV Infection

J Clin Microbiol. 2018 Mar 26;56(4):e01040-17. doi: 10.1128/JCM.01040-17. Print 2018 Apr.

Abstract

The clinical utility of the QuantiFERON-CMV (QFN-CMV) assay in heart transplant recipients was assessed. Forty-four cytomegalovirus (CMV)-seropositive patients were enrolled: 17 received antiviral prophylaxis, and 27 were managed preemptively. CMV-DNAemia monitoring was performed by the use of a quantitative real-time PCR assay. The QFN-CMV assay was retrospectively performed on blood samples collected at five posttransplant time points. A higher proportion of patients with an indeterminate QFN-CMV result after the suspension of prophylaxis than of patients who showed a global T-cell responsiveness developed CMV infection (P = 0.036). Patients who reconstituted a CMV-specific response following the first CMV-DNAemia-positive result (42.9%) showed a median CMV-DNAemia peak 1 log of magnitude lower than that seen with patients with indeterminate results, and all controlled viral replication spontaneously. The 25% of patients with an indeterminate result developed CMV disease. In the preemptive strategy group, no differences in the development of subsequent infection, magnitude of viral load, and viral control were observed on the basis of QFN-CMV measurements performed before and after the first CMV-DNAemia-positive result. Considering both CMV prevention strategies, viral relapse was associated with the failure to reconstitute CMV-specific cell-mediated immunity (CMI) after the resolution of the first episode of CMV infection (P = 0.032). QFN-CMV measurements can be a useful tool for identifying patients (i) at higher risk of developing infection after discontinuing antiviral prophylaxis, (ii) with late CMV infection who would benefit from appropriate antiviral interventions, and (iii) at higher risk of viral relapses. QFN-CMV measurements taken within 1 month posttransplantation (early period) are not revealing.

Keywords: CMV DNAemia; cell-mediated immunity; cytomegalovirus; cytomegalovirus prevention strategies; heart transplant.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / prevention & control
  • DNA, Viral / blood*
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Female
  • Heart Transplantation / adverse effects*
  • Humans
  • Immunity, Cellular*
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Monitoring, Immunologic / instrumentation
  • Monitoring, Immunologic / methods*
  • Real-Time Polymerase Chain Reaction / methods
  • Retrospective Studies
  • Transplant Recipients
  • Valganciclovir / administration & dosage
  • Valganciclovir / therapeutic use
  • Viral Load
  • Viremia
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Valganciclovir