Division of Internal Medicine, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
Clin Transplant. 2021 Nov;35(11):e14401. doi: 10.1111/ctr.14401. Epub 2021 Oct 28.
Letermovir (LTV) might be an alternative treatment to nephrotoxic foscarnet (FOS) in Ganciclovir (GCV) resistant cytomegalovirus (CMV) infection. However, its efficacy in controlling active CMV viremia is unclear, as it is only approved for CMV prophylaxis in hematopoietic stem-cell transplantation.
This case series describes 14 kidney transplant recipients (KTR) with moderate-level GCV resistant CMV infection, treated by different step-down strategies after initial FOS therapy: (1) Observation without antiviral follow-up or switch to valganciclovir (VGCV) (pre-LTV era), and (2) Switch to LTV±VGCV (LTV era).
One patient died under FOS. Thirteen patients were followed under step-down regimens. All but two patients had ongoing CMV viremia when stopping FOS. In pre-LTV era, 5/9 (56%) experienced a CMV breakthrough > 10 000 IU/ml calling for another course of FOS, as compared to 1/4 (25%) in the LTV era. Addition of VGCV to LTV at low-level viral breakthrough, addressing a possible developing resistance against LTV, prevented viral surge in two patients. In the pre-LTV era, CMV-related death or graft loss occurred in three of nine (33%), compared to no death or graft loss in the LTV era.
A step-down strategy combining LTV+VGCV, might allow to safely stop FOS at ongoing low-level viremia.
更昔洛韦(LTV)可能是一种替代膦甲酸(FOS)治疗更昔洛韦耐药巨细胞病毒(CMV)感染的方法。然而,其在控制活动性 CMV 血症方面的疗效尚不清楚,因为它仅被批准用于造血干细胞移植的 CMV 预防。
本病例系列描述了 14 例肾移植受者(KTR)患有中度水平的更昔洛韦耐药 CMV 感染,在初始 FOS 治疗后采用不同的降级策略治疗:(1)无抗病毒随访或换用缬更昔洛韦(VGCV)的观察(LTV 前时代),和(2)换用 LTV±VGCV(LTV 时代)。
1 例患者在 FOS 治疗下死亡。13 例患者接受降级方案治疗。除 2 例外,所有患者在停止 FOS 时均持续存在 CMV 血症。在 LTV 前时代,9/13(56%)例患者出现>10000 IU/ml 的 CMV 突破,需要再次使用 FOS,而 LTV 时代仅为 1/4(25%)例。在低病毒突破时,将 LTV 与 VGCV 联合使用,以预防针对 LTV 的潜在耐药性,可防止 2 例患者的病毒激增。在 LTV 前时代,9/13 例(33%)患者因 CMV 相关死亡或移植物丢失,而 LTV 时代无死亡或移植物丢失。
联合 LTV+VGCV 的降级策略可能可以在持续低病毒血症时安全停止 FOS。