The use of sirolimus in ganciclovir-resistant cytomegalovirus infections in renal transplant recipients

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.