Division of Infectious Diseases, William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
Curr Opin Infect Dis. 2018 Aug;31(4):286-291. doi: 10.1097/QCO.0000000000000459.
Cytomegalovirus (CMV) infection is a common opportunistic infection after allogeneic haematopoietic stem cell transplantation (HSCT). CMV surveillance-preemptive therapy is the current preferred approach for preventing CMV disease after HSCT. In contrast, antiviral prophylaxis is not commonly used due to myelosuppressive effects of valganciclovir. In this article, the role of the newly approved antiviral compound, letermovir, is reviewed.
Letermovir inhibits CMV by interfering viral terminase complex. In a phase 3 randomized placebo-controlled clinical study that enrolled 495 CMV-seropositive HSCT recipients, the primary end point of clinically significant CMV infection was significantly reduced by letermovir prophylaxis. Letermovir was well tolerated without risk of myelotoxicity and nephrotoxicity. Experimental in-vitro data suggest that letermovir may possess low genetic barrier to resistance. In prophylaxis trials, two breakthrough infections were reported due to selection of CMV UL56 V236M mutation.
Letermovir is an important addition to the current strategies for CMV prevention after allogeneic HSCT. Its favourable efficacy and safety profile re-opens door for antiviral prophylaxis another first-line option, similar to CMV surveillance-preemptive therapy, for preventing CMV in allogeneic HSCT recipients.
巨细胞病毒（CMV）感染是异基因造血干细胞移植（HSCT）后常见的机会性感染。CMV 监测-抢先治疗是目前预防 HSCT 后 CMV 疾病的首选方法。相比之下，由于缬更昔洛韦的骨髓抑制作用，抗病毒预防并不常用。本文回顾了新批准的抗病毒药物乐特韦的作用。
乐特韦通过干扰病毒终止酶复合物来抑制 CMV。在一项纳入 495 例 CMV 血清阳性 HSCT 受者的 3 期随机安慰剂对照临床试验中，乐特韦预防组的主要终点即临床显著的 CMV 感染显著减少。乐特韦耐受性良好，无骨髓毒性和肾毒性风险。实验室内数据表明，乐特韦可能具有较低的耐药遗传屏障。在预防试验中，报告了两例因选择 CMV UL56 V236M 突变而导致的突破性感染。
乐特韦是异基因 HSCT 后 CMV 预防策略的重要补充。其良好的疗效和安全性为抗病毒预防重新打开了大门，使其成为与 CMV 监测-抢先治疗类似的预防异基因 HSCT 受者 CMV 的一线选择。
