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心脏移植受者更昔洛韦预防巨细胞病毒的实际应用。

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

机构信息

CHU Lille, Service Universitaire de Maladies Infectieuses, Lille, France.

Univ. Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, Lille, France.

出版信息

Clin Transplant. 2024 May;38(5):e15327. doi: 10.1111/ctr.15327.

Abstract

INTRODUCTION

Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR).

METHODS

In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen.

RESULTS

The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir.

CONCLUSION

This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

摘要

简介

巨细胞病毒(CMV)仍然是实体器官移植(SOT)后主要的机会性感染。虽然缬更昔洛韦是 CMV 预防的首选药物,但由于发生细胞减少的风险,其应用可能受到限制。来特莫韦是一种新型药物,已批准用于异基因造血干细胞移植受者和高危肾移植受者的 CMV 预防,其毒性降低。本研究旨在介绍来特莫韦作为心脏移植受者(HTR)CMV 一级和二级预防的实际应用。

方法

在这项观察性、回顾性、单中心研究中,我们纳入了 2020 年 6 月至 2022 年 1 月期间接受来特莫韦预防 CMV 的所有连续成年 HTR。我们记录了 CMV 突破感染的情况、与来特莫韦相关的副作用、从缬更昔洛韦转为来特莫韦后中性粒细胞减少症的变化,以及与免疫抑制方案的任何药物相互作用。

结果

该研究纳入了 10 例患者:2 例因 CMV 感染风险高(供者阳性、受者阴性血清学状态)而接受来特莫韦一级预防,8 例因 CMV 感染而接受二级预防。来特莫韦的中位给药时间为 8 个月(范围 3-12 个月)。在预防期间未报告 CMV 突破感染。然而,在停止来特莫韦预防后,有 3 例患者发生 CMV 突破感染(30%)。未观察到明显的副作用,但有 1 例患者报告有消化不耐受。在 9 例使用他克莫司的患者中,6 例在转为来特莫韦后需要减少剂量。

结论

这项真实世界的研究似乎支持来特莫韦预防在 HTR 中的有效性。然而,治疗停止后 CMV 感染的风险值得注意。需要进一步监测药物并研究来特莫韦在 SOT 患者中预防 CMV 的疗效。

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