Gnann John W, Sköldenberg Birgit, Hart John, Aurelius Elisabeth, Schliamser Silvia, Studahl Marie, Eriksson Britt-Marie, Hanley Daniel, Aoki Fred, Jackson Alan C, Griffiths Paul, Miedzinski Lil, Hanfelt-Goade Diane, Hinthorn Daniel, Ahlm Clas, Aksamit Allen, Cruz-Flores Salvador, Dale Ilet, Cloud Gretchen, Jester Penelope, Whitley Richard J
University of Alabama at Birmingham.
Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
Clin Infect Dis. 2015 Sep 1;61(5):683-91. doi: 10.1093/cid/civ369. Epub 2015 May 8.
Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority.
Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint.
The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group.
Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.
NCT00031486.
尽管阿昔洛韦（ACV）治疗已被证实有效，但单纯疱疹性脑炎（HSE）仍会导致严重的发病率和死亡率。在接受ACV治疗的HSE患者中，死亡率约为14%-19%。在幸存者中，45%-60%在1年后有神经心理学后遗症。因此，改进HSE的治疗方法仍然是当务之急。
87例成年HSE患者（脑脊液中单纯疱疹病毒DNA聚合酶链反应[PCR]阳性确诊）在完成标准疗程的静脉ACV治疗后，被随机分为两组，一组接受伐昔洛韦（VACV）每日3次、每次2g（n = 40），另一组接受安慰剂片（n = 47），疗程90天（每天12片研究药物）。主要终点是12个月时无神经心理学损害或仅有轻度神经心理学损害的生存情况，通过马蒂斯痴呆评定量表（MDRS）进行测量。采用逻辑回归评估与主要终点相关的因素。
两个随机分组组的人口统计学特征在统计学上相似，年龄、性别或种族方面无显著差异。12个月时，VACV治疗组与安慰剂组的MDRS评分无显著差异，分别有85.7%和90.2%的患者无神经心理学损害或仅有轻度神经心理学损害（P = 0.72）。两个治疗组均未遇到与研究相关的显著不良事件。
对于PCR确诊的HSE患者，在静脉注射ACV进行标准治疗后，额外3个月的口服VACV治疗在12个月后对功能相对良好的幸存者群体进行神经心理学测试时，未显示出额外益处。
NCT00031486。
