Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients
Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients
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DOI：
10.1111/j.1399-3062.2010.00550.x
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发表时间：
2010-12-01
影响因子：
2.6
通讯作者：
Villano, S.
中科院分区：
文献类型：
--
作者：
Avery, R. K.;Marty, F. M.;Villano, S.
尽管巨细胞病毒（CMV）的预防和治疗取得了进展，但一些移植受者仍会发生难治性CMV感染. Maribavir（MBV）是一种正在研究的苯并咪唑类抗病毒药物，其作用机制与现有抗CMV药物不同。以前的I期和II期研究已经证明了MBV的有利的安全性，但其效用在治疗复杂的CMV综合征是unknow.MethodsBetween 2008年6月和12月，MBV被释放用于根据个人的紧急调查新药申请治疗医生的要求，并批准了美国食品和药物管理局和当地机构审查委员会。6例（5个实体器官移植受体和造血干细胞移植受体）谁没有响应其他疗法和/或已知的更昔洛韦耐药CMV治疗MBV在起始口服剂量为400毫克，每日两次。ResultsPatients治疗中位数为207天（范围，15-376）。6例患者中有4例在开始MBV治疗的6周内未检测到CMV DNA血症。1例患者的初始病毒载量为180万拷贝/mL，发生了MBV耐药突变。1例血清MBV水平较低的患者出现持续性CMV DNA血症和病毒尿，但未出现对MBV的基因型或表型耐药。1例患者清除了CMV DNA血症，但死于肺炎和多器官衰竭。没有显着的不良反应归因于MBVwere observed.ConclusionsMBV值得进一步系统评价CMV感染的治疗是耐药和/或难治的标准疗法，但其最佳剂量，治疗时间，并使用组合与作为一个单一的代理商尚未确定。
P>BackgroundDespite advances in cytomegalovirus (CMV) prophylaxis and therapy, some transplant recipients still develop refractory CMV infections. Maribavir (MBV), an investigational benzimidazole antiviral agent, acts by a mechanism different from that of existing anti-CMV drugs. Previous Phase I and II studies have demonstrated a favorable safety profile for MBV, but its utility in treatment of complex CMV syndromes is unknown.MethodsBetween June and December 2008, MBV was released for use under individual emergency investigational new drug applications requested by treating physicians and approved by the US Food and Drug Administration and local institutional review boards. Six patients (5 solid organ transplant recipients and 1 hematopoietic stem cell transplant recipient) who had failed to respond to other therapies and/or had known ganciclovir-resistant CMV were treated with MBV at a starting oral dose of 400 mg twice daily.ResultsPatients were treated for a median of 207 days (range, 15-376). Four of 6 patients had no detectable CMV DNAemia within 6 weeks of starting MBV therapy. One patient, who had an initial viral load of 1.8 million copies/mL, developed MBV resistance mutations. One patient, who had low serum levels of MBV, had persistent CMV DNAemia and viruria without developing genotypic or phenotypic resistance to MBV. One patient cleared CMV DNAemia, but died of pneumonia and multiorgan failure. No significant adverse effects attributable to MBV were observed.ConclusionsMBV deserves further systematic evaluation as treatment for CMV infection that is resistant and/or refractory to standard therapies, but its optimal dose, duration of therapy, and use in combinations versus as a single agent have yet to be determined.