Effect of delaying prophylaxis against CMV in D+/R- solid organ transplant recipients in the development of CMV-specific cellular immunity and occurrence of late CMV disease

J Infect. 2015 Nov;71(5):561-70. doi: 10.1016/j.jinf.2015.06.013. Epub 2015 Jul 14.

Abstract

Objectives: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT).

Methods: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models.

Results: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09).

Conclusions: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.

Keywords: CMV disease; CMV-specific cellular immunity; D+/R−; Delayed CMV prophylaxis.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Cytomegalovirus / drug effects
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / prevention & control*
  • Cytomegalovirus Infections / virology
  • Female
  • Ganciclovir / therapeutic use*
  • Humans
  • Immunity, Cellular
  • Incidence
  • Liver Transplantation
  • Male
  • Middle Aged
  • Postoperative Complications / prevention & control*
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Spain / epidemiology
  • Survival Analysis
  • Transplant Recipients*

Substances

  • Antiviral Agents
  • Ganciclovir