Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

Am J Transplant. 2016 Aug;16(8):2384-94. doi: 10.1111/ajt.13781. Epub 2016 Apr 8.

Abstract

Universal prophylaxis for cytomegalovirus (CMV) prevention is viable but, compared with a preemptive strategy, leads to higher incidence of late-onset disease (LOD) associated with poor patient and graft survival. The purpose of this study was to compare LOD with early onset disease (EOD), with a focus on the highest risk kidney transplant recipients (KTRs): CMV seronegative recipients transplanted from seropositive donors (D+R-). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vδ2-negative (Vδ2(neg) ) γδ T cell expansion involved in CMV infection resolution. EOD was defined as occurring <3 mo and LOD as occurring >3 mo after transplantation. Depending on the period, universal prophylaxis or preemptive treatment was used. Overall, 168 D+R- KTRs were included between 2003 and 2011. LOD was associated with a lower peak DNAemia (p = 0.04), fewer recurrences (odds ratio 0.16; 95% confidence interval 0.05-0.55; p = 0.01) and shorter anti-CMV curative treatment (40 vs. 60 days, p < 0.0001). As a corollary, we found that Vδ2(neg) γδ T cell expansion was faster in LOD than in EOD (31 vs. 168 days after the beginning of CMV disease, p < 0.0001). In D+R- KTRs, universal prophylaxis is associated with more LOD, which had better infection management and a faster immune response. These results support the use of universal prophylaxis over a preemptive strategy and reappraise outcomes of LOD.

Keywords: clinical research/practice; complication: infectious; immunobiology; infection and infectious agents; infectious disease; kidney transplantation/nephrology; monitoring: immune; recurrent disease; translational research/science; viral: Cytomegalovirus (CMV).

MeSH terms

  • Age of Onset
  • Antiviral Agents / pharmacology*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • Humans
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tissue Donors

Substances

  • Antiviral Agents