Effect of mTOR inhibitors during CMV disease in kidney transplant recipients: Results of a pilot retrospective study

Microbiol Immunol. 2020 Jul;64(7):520-531. doi: 10.1111/1348-0421.12794. Epub 2020 Apr 30.

Abstract

mTOR inhibitors exert a preventive effect on cytomegalovirus (CMV) disease in CMV seropositive (R+) kidney transplant recipients, but their impact during the curative treatment of CMV disease in high-risk kidney transplant recipients has not been investigated. We aimed to evaluate the efficacy and tolerance of mTOR inhibitors compared with mycophenolic acid in 63 consecutive kidney transplant recipients (80% of D+R-) suffering from CMV disease with a persistent or a recurrent CMV DNAemia. In this monocentric retrospective study, 16 had their treatment converted to mTOR inhibitors and 47 did not. The Kaplan-Meier curves did not show any significant differences in CMV DNAemia eradication (77% vs. 88% respectively; hazard ratio (HR), 1.648 [95% confidence interval (CI), 0.913-2.973]; log-rank test, P = .132), DNAemia recurrence (36% vs. 47%; HR, 1.517 [95% CI, 0.574-4.007]; log-rank test, P = .448) and CMV clinical recurrence (17% vs. 27%; HR, 1.375 [95% CI, 0.340-5.552]; log-rank test, P = .677) between patients who received mTOR inhibitors and those who did not. These results were confirmed in uni- and multivariate time-dependent Cox regressions. In summary, conversion from mycophenolic acid to mTOR inhibitors seems inadequate for improving CMV clearance or in better preventing CMV recurrences during severe or persistent CMV disease.

Keywords: CMV persistence; CMV recurrence; cytomegalovirus; kidney transplantation; mTOR inhibitors.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / prevention & control*
  • Female
  • Humans
  • Immunophenotyping
  • Kidney Transplantation / adverse effects
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Protein Kinase Inhibitors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Mycophenolic Acid