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[西多福韦(Vistide)治疗艾滋病相关进行性多灶性白质脑病。文献综述及2例报告]

[Cidofovir (vistide) in therapy of progressive multifocal leukoencephalopathy in AIDS. Review of the literature and report of 2 cases].

作者信息

Happe S, Besselmann M, Matheja P, Rickert C H, Schuierer G, Reichelt D, Husstedt I W

机构信息

Klinik und Poliklinik für Neurologie, Westfälische Wilhelms-Universität Münster.

出版信息

Nervenarzt. 1999 Oct;70(10):935-43. doi: 10.1007/s001150050601.

DOI:10.1007/s001150050601
PMID:10554789
Abstract

The progressive multifocal leukoencephalopathy (PML), a complication of the acquired immunodeficiency syndrome (AIDS) in 4%-5% of all cases, is an encephalitis caused by the JC papovavirus. The prognosis is very poor with a mean survival time after diagnosis of 3 to 6 months. No effective therapy is known to date. Therapeutic trials in small groups of patients with alpha-interferon, didanosine, and arabinoside were of minor success. A controlled study with cytarabine did not show any efficacy. Single case reports on a therapy with cidofovir (Vistide), an approved nucleotide-analogone in the therapy of cytomegalovirus-retinitis in AIDS-patients without renal dysfunction, showed positive results. We describe 2 more cases of a therapy of cidofovir in AIDS-associated PML. Out of 22 cases described in the literature, including these 2 cases, with a therapy of cidofovir in AIDS-associated PML, 16 patients improved under therapy, 2 remained stable, and only 4 patients still worsened fulminantly. These results indicate an additive antiviral effect of cidofovir against JC-virus. This may be used in the therapy of PML in AIDS-patients because no alternative antiviral therapy of PML is available at present. The efficacy of cidofovir for the therapy of PML is suggested by case reports. The exact mechanisms leading to an improvement under a therapy with cidofovir in the 16 cases described so far should be evaluated in a randomised, controlled study with an adequate size of cohorts.

摘要

进行性多灶性白质脑病(PML)是获得性免疫缺陷综合征(AIDS)的一种并发症,在所有病例中占4% - 5%,是由JC多瘤病毒引起的脑炎。其预后非常差,诊断后的平均生存时间为3至6个月。迄今为止,尚无有效的治疗方法。对少数患者使用α - 干扰素、去羟肌苷和阿糖腺苷进行的治疗试验成效甚微。一项使用阿糖胞苷的对照研究未显示出任何疗效。关于使用西多福韦(Vistide)进行治疗的单例报告显示出阳性结果,西多福韦是一种已获批用于治疗无肾功能障碍的艾滋病患者巨细胞病毒性视网膜炎的核苷酸类似物。我们描述了另外2例使用西多福韦治疗艾滋病相关PML的病例。在文献报道的包括这2例在内的22例使用西多福韦治疗艾滋病相关PML的病例中,16例患者在治疗后病情改善,2例保持稳定,只有4例患者病情仍急剧恶化。这些结果表明西多福韦对JC病毒具有附加抗病毒作用。由于目前尚无其他治疗PML的抗病毒方法,因此可将其用于艾滋病患者PML的治疗。病例报告提示了西多福韦治疗PML的疗效。对于目前所描述的16例在西多福韦治疗下病情改善的确切机制,应通过一项具有足够队列规模的随机对照研究进行评估。

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[Cidofovir (vistide) in therapy of progressive multifocal leukoencephalopathy in AIDS. Review of the literature and report of 2 cases].[西多福韦(Vistide)治疗艾滋病相关进行性多灶性白质脑病。文献综述及2例报告]
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Cidofovir added to HAART improves virological and clinical outcome in AIDS-associated progressive multifocal leukoencephalopathy.在高效抗逆转录病毒治疗(HAART)基础上加用西多福韦可改善艾滋病相关进行性多灶性白质脑病的病毒学和临床结局。
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Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythematosus and progressive multifocal leukoencephalopathy.西多福韦使一名系统性红斑狼疮合并进行性多灶性白质脑病患者脑脊液中 JC 病毒基因组转阴
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引用本文的文献

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Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.进行性多灶性白质脑病,即人类大脑中由 JC 病毒引起的脱髓鞘疾病的分子生物学、流行病学和发病机制。
Clin Microbiol Rev. 2012 Jul;25(3):471-506. doi: 10.1128/CMR.05031-11.
2
Smoldering myeloma presenting as progressive multifocal leukoencephalopathy: a case report.以进行性多灶性白质脑病为表现的冒烟型骨髓瘤:一例报告
J Med Case Rep. 2012 Jul 2;6:177. doi: 10.1186/1752-1947-6-177.
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Molecular regulation of JC virus tropism: insights into potential therapeutic targets for progressive multifocal leukoencephalopathy.
JC 病毒嗜性的分子调控:对进行性多灶性白质脑病潜在治疗靶点的深入了解。
J Neuroimmune Pharmacol. 2010 Sep;5(3):404-17. doi: 10.1007/s11481-010-9203-1. Epub 2010 Apr 17.
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Cidofovir in combination with HAART and survival in AIDS-associated progressive multifocal leukoencephalopathy.
J Neurol. 2008 Apr;255(4):526-31. doi: 10.1007/s00415-008-0731-z. Epub 2008 Jan 18.
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The relative contributions of HAART and alpha-interferon for therapy of progressive multifocal leukoencephalopathy in AIDS.高效抗逆转录病毒疗法(HAART)与α干扰素在艾滋病相关进行性多灶性白质脑病治疗中的相对作用。
J Neurovirol. 2001 Aug;7(4):353-7. doi: 10.1080/13550280152537238.
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