Budde Klemens, Kamar Nassim, Crespo Marta, Small Catherine B, Stauffer Nicole, Broyde Natalya, Gilbert Christopher L, Moise Pamela, Haber Barbara
Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Nephrology and Organ Transplantation, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), and Paul Sabatier University, Toulouse, France.
Am J Transplant. 2025 Jul 21. doi: 10.1016/j.ajt.2025.07.2471.
This post-hoc analysis was conducted to understand the impact of kidney function on 200 days of cytomegalovirus (CMV) prophylaxis in CMV donor-positive/recipient-negative (D+R-) kidney transplant recipients (KTRs). Adult CMV D+R- KTRs were randomized (1:1) post-transplant to letermovir 480 mg (with acyclovir and valganciclovir placebo) or valganciclovir 900 mg (with acyclovir and letermovir placebos) daily for 28-weeks (NCT03443869). Valganciclovir and acyclovir doses were modified for kidney function (Cockcroft-Gault creatinine clearance [CrCl]). Dose frequency, adherence, CMV DNAemia, and discontinuations were evaluated at week 28. 480 CMV D+R- KTRs had a median CrCl of 67 mL/min. All participants taking letermovir (or letermovir placebo) received daily dosing (i.e., no intermittent dosing), whereas approximately 50% of participants receiving valganciclovir (or valganciclovir placebo) received intermittent dosing (i.e., every 2 days or twice weekly titrated to CrCl). Kidney function did not impact adherence, quantifiable CMV DNAemia, or prophylaxis discontinuation in the letermovir group; however, adherence was lower, and quantifiable CMV DNAemia and discontinuation occurred more frequently in the valganciclovir group, particularly among those with lower kidney function post-transplant. In CMV D+R- KTRs, letermovir prophylaxis was associated with less CMV DNAemia compared to valganciclovir in participants with low kidney function during the 200-day prophylaxis period. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT03443869, EudraCT: 2017-001055-30.
进行这项事后分析是为了了解肾功能对巨细胞病毒（CMV）供体阳性/受体阴性（D+R-）肾移植受者（KTRs）200天CMV预防的影响。成年CMV D+R- KTRs在移植后随机（1:1）分为每日服用480毫克来特莫韦（联合阿昔洛韦和缬更昔洛韦安慰剂）或900毫克缬更昔洛韦（联合阿昔洛韦和来特莫韦安慰剂），持续28周（NCT03443869）。根据肾功能（Cockcroft-Gault肌酐清除率[CrCl]）调整缬更昔洛韦和阿昔洛韦的剂量。在第28周评估给药频率、依从性、CMV血症和停药情况。480例CMV D+R- KTRs的CrCl中位数为67 mL/分钟。所有服用来特莫韦（或来特莫韦安慰剂）的参与者均接受每日给药（即无间歇给药），而接受缬更昔洛韦（或缬更昔洛韦安慰剂）的参与者中约50%接受间歇给药（即每2天或每周两次，根据CrCl调整剂量）。肾功能对来特莫韦组的依从性、可量化的CMV血症或预防停药无影响；然而，缬更昔洛韦组的依从性较低，可量化的CMV血症和停药更频繁发生，尤其是移植后肾功能较低的患者。在CMV D+R- KTRs中，在200天预防期内，与缬更昔洛韦相比，来特莫韦预防在肾功能低下的参与者中与较少的CMV血症相关。临床试验注册：ClinicalTrials.gov：NCT03443869，EudraCT：2
