#1569 Cytomegalovirus (CMV) infection in renal transplant patients managed with early pre-emptive treatment
Authors: Anyu Anawinla Ta , Lucey Mary , Jones Gareth , Harber Mark , Hart Jennifer , Irish Dianne , Haque Tanzina 
Published: May 2024

Abstract

Background and Aims
Human Cytomegalovirus (CMV) can cause significant morbidity in transplant recipients. Primary CMV infection in CMV seronegative recipients (R−) and reactivation of CMV in seropositive recipients (R+) post-transplant can lead to CMV end organ disease (EOD).
At Royal Free Hospital (RFH), London, United Kingdom, CMV EOD is prevented through pre-emptive therapy (PET), which utilises quantitative real-time PCR (qPCR) in whole blood to monitor all transplant patients and guide therapeutic interventions (1). PET is started in D+R− transplant patients following the first detectable CMV DNA (≥200 copies/ml) in blood (2). For CMV seropositive patients, PET is started when CMV DNA is ≥3000 copies/ml. This differs from many transplant centres which provide CMV anti-viral prophylaxis for the first 3-6 months post-transplant to patients at high risk of developing CMV EOD.
In this observational study, the effectiveness of our PET approach and differences in CMV viral replication kinetics was retrospectively analysed in renal transplant recipients of differing CMV serostatus.

Method
A retrospective review of results from electronic patient records and laboratory information management system for patients who underwent renal transplantation from April 2021 to January 2023 was conducted.
Patients were divided into four groups based on organ donor and recipient CMV IgG serostatus (D+R−, D+R+, D−R+, D−R−). Those who were followed up for less than 90 days or had unknown donor serostatuses were excluded.

Results
A total of 227 patients who received renal transplantation between April 2021 to January 2023 were identified. Of which, 11% (25/227) were D+R−, 42.3% (96/227) were D+R+, 33% (75/227) were D−R+ and 13.7% (31/227) were D−R−.
Within each group, 60% (15/25) of D+R−, 61.5% (59/96) of D+R+ and 48% (36/75) of D−R+ patients developed CMV viraemia during the monitoring period. Of CMV viraemic patients, all D+R− (15/15), 54.2% (32/59) of D+R+ and 27.8% (10/36) of D−R+ patients were treated with valganciclovir as per our PET protocol. None of the D−R− patients developed any CMV viraemia. The mean peak viral load for patients with viraemia requiring treatment with valganciclovir was 4772 copies/ml (range 210-30000 copies/ml) in D+R−, 5050 copies/ml (range 3000-30000 copies/ml) and 5050 copies/ml (range 3300-18000 copies/ml) in D+R+ and D−R+ groups respectively.
The mean time to first viraemia was 59 days (range 15-332) for the D+R−, 40 days (range 7-177) for D+R+ and 43 days (range 15-91) for D−R+ patients. Furthermore, the mean duration of viraemia was 34 days for D+R−, 37.5 days for D+R+ and 30.5 days for D−R+ groups. 19 patients had CMV viraemia recurrence requiring re-treatment, 63%were D+R− (12/19), 32% were D+R+ (6/19) and 5% (1/19) were D−R+.
Across all four groups, two patients developed CMV EOD. One D+R+ patient was found to have CMV in respiratory sample and one D−R+ patient had CMV on colon biopsy. One D+R− patient developed UL97 mutations (M460I and A594V) conferring ganciclovir resistance due to poor compliance and was treated with maribavir.

Conclusion
PET is a safe and effective approach which reduces the risk of CMV EOD and antiviral medication resistance in SOT patients. Our PET approach provides monitoring of all patients regardless of CMV serostatus thereby reducing the risk of CMV EOD in all patients by ensuring early treatment of viraemia.