Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte proliferation and activation in renal transplant recipients

Antivir Ther. 2011;16(8):1227-35. doi: 10.3851/IMP1879.

Abstract

Background: Antiviral prophylaxis against cytomegalovirus has been associated with reduced risk of allograft rejection and improved allograft survival after renal transplantation. This phenomenon might not be fully explained by preventing the indirect effects of cytomegalovirus. The effect of antiviral agents on lymphocyte function in patients treated with modern immunosuppression has not been studied to date.

Methods: Adult renal transplant recipients were assigned to 3-month prophylaxis with either valganciclovir (900 mg once daily; n=19) or valacyclovir (2 g four times daily; n=17) as part of an ongoing randomized trial. Subsets of lymphocytes, lymphocyte proliferation and/or cytokine production after in vitro mitogen stimulation were evaluated at the end of prophylaxis and 1 month after withdrawal of antiviral drugs.

Results: Lymphocyte proliferation was significantly decreased both after phytohemagglutinine (25% ±15% versus 32% ±18%; P=0.025) and concanavalin A stimulation (17% ±9% versus 25% ±16%; P=0.011) during valganciclovir, but not valacyclovir therapy. Moreover, a lower activated T-cell count (CD3(+)HLA-DR(+) cells) was noted in valganciclovir-treated patients (13% ±10% versus 17% ±12% of total CD3(+) T-cells; P=0.005).

Conclusions: Valganciclovir suppresses lymphocyte proliferation and activation in patients after renal transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / administration & dosage
  • Acyclovir / analogs & derivatives
  • Acyclovir / therapeutic use
  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / therapeutic use
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / prevention & control*
  • Cytomegalovirus Infections / virology
  • Female
  • Ganciclovir / administration & dosage
  • Ganciclovir / analogs & derivatives*
  • Ganciclovir / therapeutic use
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppression / adverse effects
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation / immunology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Valacyclovir
  • Valganciclovir
  • Valine / administration & dosage
  • Valine / analogs & derivatives
  • Valine / therapeutic use

Substances

  • Antiviral Agents
  • Immunosuppressive Agents
  • Phytohemagglutinins
  • Concanavalin A
  • Valganciclovir
  • Valine
  • Valacyclovir
  • Ganciclovir
  • Acyclovir