title: The use of sirolimus in ganciclovir-resistant cytomegalovirus infections in renal transplant recipients.
abstract: BACKGROUND
  The widespread use of prophylactic ganciclovir and anti-lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. The use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection.
  
  
  METHODS
  Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations.
  
  
  RESULTS
  Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection.
  
  
  CONCLUSIONS
  This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.
authors.affiliation: Laboratório de Imunologia Clínica e Experimental, Division of Nephrology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Kikumi Suzete
authors.initials: KS
authors.lastname: Ozaki
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
authors.forename: Eliana
authors.initials: E
authors.lastname: Nogueira
authors.forename: Mauricio Galvão
authors.initials: MG
authors.lastname: Pereira
authors.forename: Celso
authors.initials: C
authors.lastname: Granato
authors.forename: Cláudio
authors.initials: C
authors.lastname: Melaragno
authors.forename: Luis Fernando Aranha
authors.initials: LF
authors.lastname: Camargo
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D024882:Drug Resistance, Viral / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir; D020123:Sirolimus