title: Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte proliferation and activation in renal transplant recipients.
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.
authors.affiliation: Department of Internal Medicine I, Charles University in Prague, Faculty of Medicine in Pilsen, Teaching Hospital Pilsen, Pilsen, Czech Republic. reischig@fnplzen.cz
authors.forename: Tomá
authors.initials: T
authors.lastname: Reischig
authors.forename: Miroslav
authors.initials: M
authors.lastname: Prucha
authors.forename: Lenka
authors.initials: L
authors.lastname: Sedlackova
authors.forename: Daniel
authors.initials: D
authors.lastname: Lysak
authors.forename: Pavel
authors.initials: P
authors.lastname: Jindra
authors.forename: Mirko
authors.initials: M
authors.lastname: Bouda
authors.forename: Martin
authors.initials: M
authors.lastname: Matejovic
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000077483:Valacyclovir; D000077562:Valganciclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D003208:Concanavalin A; D000077562:Valganciclovir; D014633:Valine; D000077483:Valacyclovir; D015774:Ganciclovir; D000212:Acyclovir