Management and Outcome of COVID-19 Infection Using Nirmatrelvir/Ritonavir in Kidney Transplant Patients

Background Nirmatrelvir/ritonavir has been shown to reduce the risk of coronavirus disease 2019 (COVID-19)-related complications in patients at high risk for severe COVID-19. However, clinical experience of nirmatrelvir/ritonavir in the transplant recipient population is scattered due to the complex management of drug-drug interactions with calcineurin inhibitors. We describe the clinical experience with nirmatrelvir/ritonavir at The Ottawa Hospital kidney transplant program. Methods Patients who received nirmatrelvir/ritonavir between April and June 2022 were included and followed up to 30 days after completion of treatment. Tacrolimus was withheld for 24 hours and resumed 72 hours after the last dose of nirmatrelvir/ritonavir (on day 8) on the basis of the drug level the day before. The first 30 patients had their dose adjusted according to drug levels performed twice in the first week and as needed thereafter. Subsequently, a simplified algorithm with less frequent calcineurin inhibitor-level monitoring was implemented. Outcomes, including tacrolimus-level changes, serum creatinine and AKI (defined as serum creatinine increase by 30%), and clinical outcomes were described globally and compared between algorithms. Results Fifty-one patients received nirmatrelvir/ritonavir. Tacrolimus levels drawn at the first time point, 7 days after withholding of calcineurin inhibitor, and 2 days after discontinuing nirmatrelvir/ritonavir were within the therapeutic target in 17/44 (39%), subtherapeutic in 21/44 (48%), and supratherapeutic in 6/44 (14%). Two weeks after, 55% were within the therapeutic range, 23% were below, and 23% were above it. The standard and simplified algorithms provided similar tacrolimus level (median 5.2 [4.0-6.2] mu g/L versus 4.8 [4.3-5.7] mu g/L, P = 0.70). There were no acute rejections or other complications. Conclusions Withholding tacrolimus starting the day before initiation of nirmatrelvir/ritonavir with resumption 3 days after completion of therapy resulted in a low incidence of supratherapeutic levels but a short period of subtherapeutic levels for many patients. AKI was infrequent. The data are limited by the small sample size and short follow-up.