Abstract: PUB671
Metabolism Matters: An Interesting Case on Immediate Tacrolimus Metabolism in a Renal Transplant Recipient on Ritonavir-Boosted Antiretroviral Therapy
Session Information
Category: Trainee Case Report
- 1902 Transplantation: Clinical
Author
- Singh, Arvind Kumar, Derriford Hospital NHS Trust, Plymouth, Devon, United Kingdom
Group or Team Name
- Derriford Hospital Renal team
Introduction
Access to solid organ transplantation in the setting of human immunodeficiency virus (HIV) infection has been increasing. HIV positive solid organ transplant recipients are at increased risk of acute rejection – partly because of drug interactions. Multiple studies report serious interactions between tacrolimus and ritonavir-boosted HIV-1 protease inhibitors (PIs). The conventional approach is to reduce the tacrolimus dose to around ten percent of the standard dose and anticipate a ritonavir ‘washout period’ of up to ten days. Local experience managing liver transplant recipients with HCV at this centre have led to the conclusion that the interaction period is much shorter. They therefore advocate less aggressive tacrolimus dose reductions in view of the even higher risks of early rejection if tacrolimus levels are low.
Case Description
We present an interesting case of a patient undergoing haemodialysis who was matched to a deceased brain dead donor through the national organ sharing scheme in the United Kingdom. The patient was on antiretroviral therapy with ritonavir and their HIV viral load had been undetectable for several years. The HIV specialist team recommended a change to a non-tacrolimus interacting regimen at the time of transplantation.
The last dose of ritonavir was taken 40 hours before the first administration of tacrolimus. Induction was with basiliximab and maintenance therapy was with tacrolimus (Adoport), mycophenolate mofetil and prednisolone. Whole blood tacrolimus concentrations were measured at the time of first administration (standard single 0.05 mg/kg dose) and at 30, 60, 120, 240, 360, 480 and 720 minutes.
Please see the attcahed graph image below
Discussion
Although there is concern about concomitant use of ritonavir and tacrolimus, this case suggests minimal interaction only 40 hours after the last dose, with appropriate tacrolimus concentrations and an exposure to tacrolimus (area under the curve of 91.2 ng.h/mL) comparable to patients receiving tacrolimus not on ritonavir.
We conclude that if a patient on antiretroviral therapy is taken off a ritonavir-boosted protease inhibitor regimen when starting or taking tacrolimus therapy, the standard dosing should be considered at the time of the change along with close therapeutic drug monitoring.