Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients.
Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients.
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DOI：
10.1016/j.jcv.2020.104421
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发表时间：
2020-07-01
期刊：
影响因子：
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通讯作者：
Zuckerman, Mark
中科院分区：
文献类型：
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作者：
Anton-Vazquez, Vanesa;Mehra, Varun;Zuckerman, Mark
简介：方法：回顾性分析2011年6月至2019年6月间532例HSCT受者的临床资料。HSV-1阳性47例，HSV-2阳性16例。抗病毒药物的HSV耐药性的分析是在英国公共卫生参考实验室在伦敦使用表型和/或基因型耐药assays.Results：ACV耐药HSV的患病率占17%（8/48）的HSV-1感染病例。所有8例患者均接受了T细胞去除的同种异体HSCT治疗血液系统恶性肿瘤。这些患者中有一半为男性，中位年龄为57.5岁（范围：26-63岁）。慢性移植物抗宿主病（cGVHD）感染7例患者前HSV-1诊断。HSV-1感染在接受静脉注射ACV（n=2）或口服ACV（n=6例患者）预防时发生，中位时间为HSCT后373天[范围，18-2183]。在初次HSV诊断后中位25天（范围，16-109）临床怀疑ACV耐药，随后在中位25天（范围，10-59）实验室确认。所有患者均表现为ACV治疗无效的出血性口腔粘膜炎。在所有8例患者中开始膦甲酸（FOS）治疗（等待实验室确认ACV耐药），具有一定效果，但与显著的毒性负荷相关。4例患者再次出现HSV感染复发或未消退。三个复发HSV死于其他原因，而患有持续性口腔HSV lesions.CONCLUSION：一个长期的免疫抑制状态T-耗竭HSCT，同时延长使用ACV，早发性全身HSV感染，存在cGVHD，和治疗毒性的管理ACV耐药HSV感染和替代有效的抗病毒选择仍然是一个未满足的需求，在这种临床环境。
INTRODUCTION: The emergence of herpes simplex virus (HSV) resistance to aciclovir (ACV) has increasingly been reported among hematopoietic stem cell transplant (HSCT) recipients and often associated with extended ACV prophylaxis.METHODS: Between June 2011 and June 2019, medical records of 532 HSCT recipients with suspected HSV infection were retrospectively analyzed. HSV-1 and HSV-2 positive samples were identified in 47 and 16 patients respectively. Analysis of HSV resistance to antivirals was performed at the Public Health England reference laboratory in London using phenotypic and/or genotypic resistance assays.RESULTS: The prevalence of ACV-resistant HSV accounted for 17% (8/48) of infected HSV-1 cases. All 8 patients received T-cell depleted allogeneic HSCT for hematological malignancies. Half of these patients were male with a median age was 57.5 years (range; 26-63). Chronic Graft versus Host disease (cGVHD) affected 7 patients before HSV-1 diagnosis. HSV-1 infection developed while receiving either intravenous ACV (n=2) or oral ACV (n=6 patients) prophylaxis at a median of 373 [range,18-2183] days post-HSCT. ACV resistance was clinically suspected at a median of 25 [range,16-109] days after initial HSV diagnosis and subsequently laboratory confirmed at a median of 25 (range,10-59) days. All patients presented with hemorrhagic oral mucositis refractory to treatment dose ACV. Foscarnet (FOS) treatment was initiated in all 8 patients (pending laboratory confirmation of ACV resistance) with some effect but associated with significant toxicity burden. Four patients presented again with recurrent HSV infection or no resolution. Three with recurrent HSV died from other causes while suffering from persistent oral HSV lesions.CONCLUSION: A prolonged immunosuppressed state following T-deplete HSCTs alongside extended use of ACV, early onset systemic HSV infection, presence of cGVHD, and treatment toxicities pose a significant challenge to the management of ACV resistant HSV infections and alternative effective antiviral options remains an unmet need in this clinical setting.