Resistance of herpes simplex viruses to acyclovir: An update from a ten-year survey in France
Resistance of herpes simplex viruses to acyclovir: An update from a ten-year survey in France
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DOI：
10.1016/j.antiviral.2014.08.013
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发表时间：
2014-11-01
影响因子：
7.6
通讯作者：
Morfin, Florence
中科院分区：
文献类型：
--
作者：
Frobert, Emilie;Burrel, Sonia;Morfin, Florence
无环鸟苷（ACV）的广泛使用和越来越多的免疫功能低下的患者引起了对ACV耐药的单纯疱疹病毒（HSV）增加的关注。无环鸟苷耐药历来是免疫功能低下患者的主要问题，报告的频率在2.5%至10%之间。本研究的目的是重新评估2002年至2011年10年间免疫功能正常和免疫功能低下患者中HSV对ACV的耐药状况。这是通过回顾性随访1425例患者完成的。在免疫功能正常的患者中，研究期间耐药的患病率不超过0.5%;而在免疫功能低下的患者中，观察到显著增加，从2002年至2006年的3.8%（7/182例患者）上升至2007年至2011年的15.7%（28/178）（p = 0.0001）。这种耐药性的急剧上升可能主要表现为异基因造血干细胞移植患者，其中ACV耐药的患病率从2002年至2006年的14.3%（4/28）上升至2007年至2011年的46.5%（26/56）（p = 0.005）。没有发现与其他类型的免疫缺陷相关的无环鸟苷耐药性增加。HSV UL 23胸苷激酶和UL 30 DNA聚合酶基因的基因型特征分别揭示了11个和7个先前未报道的替换。这些取代可能与潜在的多态性、耐药性或其他意义不明的突变有关。(C)2014爱思唯尔有限公司版权所有。
The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011(28/178) (p = 0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p = 0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance. (C) 2014 Elsevier B.V. All rights reserved.