title: Is cytomegalovirus prophylaxis dispensable in patients receiving an mTOR inhibitor-based immunosuppression? a systematic review and meta-analysis.
abstract: BACKGROUND
  Cytomegalovirus (CMV) is a common opportunistic infection after solid organ transplantation. Cytomegalovirus causes increased morbidity, mortality, and reduced allograft survival. Prophylaxis may help control the virus but is associated with substantial side effects and does not completely prevent virus reactivation; relapses after cessation of the prophylaxis are frequent. Experimental and clinical data suggest that mTOR inhibitors may have an anti-CMV effect. Here, we present a meta-analysis of clinical trials after solid organ transplantation and describe potential mechanisms involved in the anti-CMV effect of mTOR-inhibitors.
  
  
  METHODS
  The current literature was reviewed for randomized controlled trials in solid organ transplantation comparing an mTOR-I with a non-mTOR-I (CNI based) treatment. The scientific quality of the trials was assessed by the Jadad score, the use of an effective allocation concealment (AC) and the existence of an intention-to-treat (ITT) analysis. Cytomegalovirus incidence was assessed in studies comparing 1) an mTOR-I-based with a CNI-based immunosuppression (10 trials, n=3,100 patients) and 2) an mTOR-I/CNI combination therapy with a CNI-based immunosuppression (15 trials, n=7,100 patients).
  
  
  RESULTS
  In the first meta-analysis, CMV events after solid organ transplantation occurred significantly more often under CNIs (RR=2.27). The second meta-analysis comparing the mTOR-I + CNI combination with a CNI treatment in 15 trials of kidney, heart, and liver transplantation showed again a higher CMV incidence when patients received an mTOR-I free immunosuppression (RR=2.45).
  
  
  CONCLUSIONS
  mTOR-inhibitor treatment either alone or in combination with CNIs reduces significantly the CMV incidence after organ transplantation. With the use of an mTOR-inhibitor, CMV prophylaxis may be dispensible.
authors.affiliation: Department of Surgery, University Hospital Grosshadern, Ludwig Maximilian's University, Munich Germany. joachim.andrassy@med.uni-muenchen.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Andrassy
authors.forename: Verena S
authors.initials: VS
authors.lastname: Hoffmann
authors.forename: Markus
authors.initials: M
authors.lastname: Rentsch
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangl
authors.forename: Antje
authors.initials: A
authors.lastname: Habicht
authors.forename: Bruno
authors.initials: B
authors.lastname: Meiser
authors.forename: Michael
authors.initials: M
authors.lastname: Fischereder
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Markus
authors.initials: M
authors.lastname: Guba
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D016377:Organ Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases