Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients.
Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.
Department of Nephrology, Hospital del Mar, Barcelona, Spain.|Institut Mar for Medical Research, Barcelona, Spain.|REDINREN Spanish Network for Renal Research RD12/0021, Barcelona, Spain.
Julio
J
Pascual
Clinical Biostatistics Unit, Puerta de Hierro University Hospital, Instituto de Investigacion Puerta de Hierro (IDIPHIM), Madrid, Spain.
Ana
A
Royuela
REDINREN Spanish Network for Renal Research RD12/0021, Barcelona, Spain.|Department of Nephrology, Hospital Ramón y Cajal, IRICYS, Madrid, Spain.
Ana M
AM
Fernández
Liver Unit, Clínica Universidad de Navarra, CIBERehd, IdiSNA, Pamplona, Spain.
Ignacio
I
Herrero
Department of Cardiology, Institute of Investigation 1+12, Universidad Complutense de Madrid, University Hospital 12 de Octubre, Madrid, Spain.
Juan F
JF
Delgado
Lung Transplant Unit, Hospital Universitario y Politecnico la FE, Universidad de Valencia, Valencia, Spain.
Amparo
A
Solé
REDINREN Spanish Network for Renal Research RD12/0021, Barcelona, Spain.|Department of Nephrology, Fundació Puigvert, Barcelona, Spain.
Lluis
L
Guirado
Liver Unit, University Hospital Lozano Blesa, Zaragoza, IIS Aragon, Spain.
Trinidad
T
Serrano
Clinical Unit of Infectious Diseases, Hospital Universitario Reina Sofia, IMIBIC-UCO, Córdoba, Spain.
Julián
J
de la Torre-Cisneros
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Asunción
A
Moreno
Department of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, University of Seville, Seville, Spain.
Elisa
E
Cordero
Department of Nephrology, Hospital Universitario de Gran Canaria Dr Negrin, Gran Canaria, Spain.
Roberto
R
Gallego
Unit of Infectious Diseases, Institute of Investigation 1+12, Universidad Complutense de Madrid, University Hospital 12 de Octubre, Madrid, Spain.
Carlos
C
Lumbreras
Unit of Infectious Diseases, Institute of Investigation 1+12, Universidad Complutense de Madrid, University Hospital 12 de Octubre, Madrid, Spain.
José M
JM
Aguado
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016377:Organ Transplantation / Q000009:adverse effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D066027:Transplant Recipients; D014777:Virus Diseases / Q000628:therapy*
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
cytomegalovirus; everolimus; mTOR inhibitors; sirolimus