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

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 longterm 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. K E Y W O R D S recurrent cytomegalovirus, survival, transplant S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Gardiner BJ, Chow JK, Brilleman SL, Peleg AY, Snydman DR. The impact of recurrent cytomegalovirus infection on long-term survival in solid organ transplant recipients. Transpl Infect Dis.

Assessment of infectious complications in elderly kidney transplant recipients receiving induction with anti‐thymocyte globulin vs basiliximab

“…CMV infection was defined as a positive test for CMV in any blood or non‐blood diagnostic sample and further classified into asymptomatic viremia, syndrome, or disease. CMV syndrome was defined as the presence of CMV replication in serum plus at least two of the following clinical features: new or increased malaise, fever for ≥2 days, neutropenia (<1.5 × 10 3 cells/µL), thrombocytopenia (<150 × 10 3 cells/µL), or elevated liver enzymes (AST/ALT >84/108 IU/L, respectively) . Patients with CMV end‐organ disease had clinical evidence of organ dysfunction plus laboratory confirmation of CMV.…”

Use of T Cell Mediated Immune Functional Assays for Adjustment of Immunosuppressive or Anti-infective Agents in Solid Organ Transplant Recipients: A Systematic Review

“…Infections and drug-related complications are highly prevalent and affect both the survival and quality of life of the SOT recipients (51)(52)(53)(54). Only one published interventional study used ImmuKnow R to adjust the dosage of immunosuppression in liver transplant recipients (39).…”

Role of Virus-Specific T Cell Therapy for Cytomegalovirus and BK Infections in Kidney Transplant Recipients

“…Primary infection has been associated with a myriad of negative infectious outcomes including persistence, recurrence, and resistance, which in turn affect long-term graft survival. 9 These negative outcomes are thought to be related to host inability to mount sufficient CMV-specific T cell immunity to adequately control viral replication. 10 The drug of choice for CMV prevention and treatment is intravenous ganciclovir and its oral prodrug, valganciclovir.…”