Safety, Efficacy, and Relapse of Nirmatrelvir-Ritonavir in Kidney Transplant Recipients Infected With SARS-CoV-2

Kidney Int Rep. 2022 Nov;7(11):2356-2363. doi: 10.1016/j.ekir.2022.08.026. Epub 2022 Aug 28.

Abstract

Introduction: The efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs).

Methods: In this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied.

Results: A total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads.

Conclusion: NR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.

Keywords: SARS-CoV-2; efficacy; kidney transplantation; nirmatrelvir-ritonavir; relapse; safety.