GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS DISEASE: THE TROLL OF TRANSPLANTATION
Dr Claire Johnston1, Darcy Gray2,3, Amanda Varghese1, Ana Domazetovska4, Karen Keung5, Spiros Miyakis2,3, William Pratt2, Peter Presgrave6, William Rawlinson4,7,8, Kenneth Yong5, Stanley Zhou9, Dr Jeffrey Ha1,10
1Department of Renal Medicine, Wollongong Hospital, Wollongong, Australia, 2Department of Infectious Diseases, Wollongong Hospital, Wollongong, Australia, 3Graduate School of Medicine, University of Wollongong, Wollongong, Australia, 4Serology and Virology Division (SAViD), Microbiology, NSW Health Pathology, Prince of Wales Hospital, Sydney, Australia, 5Department of Renal Medicine, Prince of Wales Hospital, Sydney, Australia, 6Department of Haematology, Wollongong Hospital, Wollongong, Australia, 7School of Biomedical Sciences, University of New South Wales, Sydney, Australia, 8School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, 9Drug & Therapeutics Committee, Department of Pharmacy, Wollongong Hospital, Wollongong, Australia, 10Renal and Metabolic Division, The George Institute for Global Health, Faculty of Medicine & Health, University of New South Wales, Sydney, Australia
Background: Infection of transplant recipients with ganciclovir-resistant cytomegalovirus (GCV-R CMV) results in longer, more costly recovery. GCV-R CMV is under-recognised in kidney transplant recipients (KTRs) and novel antiviral treatments are now available. We report three cases of GCV-R CMV disease post-kidney transplant at a tertiary hospital in regional NSW.
Methods: Two female patients aged 30 and 36 years had symptomatic CMV disease (diarrhoea and hepatitis) at 21- and 9-months post-transplant respectively. A 69-year-old female had disseminated CMV disease with CMV colitis at 12-months post-transplant complicated by Guillain-Barre syndrome. All cases were at-risk with donor-positive/recipient-negative CMV serostatus and received standard valganciclovir prophylaxis (doses adjusted using Cockcroft-Gault formula) for 200 days following induction therapy. Patient weights varied considerably (35kg, 68kg, and 106kg). GCV-R CMV was detected within 6 months of initially ganciclovir-responsive CMV disease in two cases, including detection at 4 months following ATG therapy for T cell mediated rejection in the remaining case. All three experienced post-transplant neutropaenia. Following GCV-R CMV detection, patients were treated with reduced immunosuppression and CMV-specific immunoglobulin. Maribavir was used in two cases, resulting in complete viral load suppression. Maribavir was administered as a bridge to adoptive T cell therapy in 69-year-old female with history of life-threatening CMV disease. All cases are planned for secondary CMV prophylaxis with functioning grafts.
Conclusions: These cases highlight: efficacy of maribavir to treat GCV-R CMV in KTRs; importance of its early recognition; need for strategies for its prevention; and the challenges in (val)ganciclovir dosing for CMV prophylaxis/treatment at extremes of weight while evidence for ganciclovir therapeutic drug monitoring remains limited.
Biography:
Jeffrey is a nephrologist at Wollongong Hospital and a postdoctoral research fellow at The George Institute for Global Health, UNSW Sydney. His PhD thesis entitled “Cardiovascular risk in chronic kidney disease” has informed international guidelines and the management of cardiovascular disease in patients with CKD. He is also a former Editorial Intern with the American Journal of Kidney Diseases.