The impact of recurrent cytomegalovirus infection on long-term survival in solid organ transplant recipients

Transpl Infect Dis. 2019 Dec;21(6):e13189. doi: 10.1111/tid.13189. Epub 2019 Oct 18.

Abstract

Background: Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid organ transplantation (SOT). While recurrent infection occurs in up to 30% of patients, its impact on mortality is unclear. The aim of this study was to explore the relationship between recurrent CMV infection and long-term survival in SOT recipients.

Methods: We performed a retrospective cohort study of SOT recipients who completed treatment for an episode of CMV infection. Patients were followed until death, loss to follow-up or 10 years following CMV treatment completion. Univariable and multivariable hazard ratios (HR) were calculated, treating relapse and rejection following CMV as time-varying.

Results: About 79 kidney, 52 heart, 34 liver, and 5 liver-kidney transplant recipients were included. About 62/170 died, at a median of 3.8 years (IQR 0.8-6.6 years). Median follow-up among the 108 survivors was 7.4 years (IQR 3.7-10 years). Recurrent CMV infection occurred in 49/170 (29%), 67% within 6 months of treatment completion. Mortality among those who relapsed was 39% (19/49) vs 36% (43/121) in those who remained relapse-free (unadjusted HR 1.59, 95% CI 0.92-2.75, P = .10). After adjusting for age and transplanted organ, findings were similar (HR 1.68, 95% CI 0.93-3.04, P = .09).

Conclusions: Mortality following CMV remains high even in the valganciclovir era. Although our findings suggest a possible increased risk of death among patients with recurrent CMV, these did not reach statistical significance. The complex nature of these patients, multiple potential confounders, and limited statistical power made detection of small effects difficult. Larger prospective studies evaluating the clinical impact of strategies to reduce recurrence are needed.

Keywords: recurrent cytomegalovirus; survival; transplant.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotic Prophylaxis / statistics & numerical data
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / mortality*
  • Cytomegalovirus Infections / prevention & control
  • Cytomegalovirus Infections / virology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mortality / trends*
  • Organ Transplantation / adverse effects*
  • Recurrence
  • Retrospective Studies
  • Secondary Prevention / statistics & numerical data
  • Survival Analysis
  • Transplant Recipients / statistics & numerical data*
  • Valganciclovir / therapeutic use
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Valganciclovir