Arendt Gabriele, Nolting Thorsten, Frisch Christian, Husstedt Ingo-Wilhelm, Gregor Nora, Koutsilieri Eleni, Maschke Mattias, Angerer Alexander, Obermann Mark, Neuen-Jacob Eva, Adams Ortwin, Loeffert Sabine, Riederer Peter, ter Meulen Volker, Sopper Sieghart
Department of Neurology, University Hospital of Dusseldorf (UKD), Dusseldorf, Germany.
J Neurovirol. 2007 Jun;13(3):225-32. doi: 10.1080/13550280701315355.
The objectives of this study is to clarify whether there are phases critical for the infection of the central nervous system (CNS) as defined by active viral replication in the cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV) infection. One hundred and nine HIV-1-positive homo- and bisexual patients in early and late disease stages with or without highly active antiretroviral therapy (HAART) were included in the cross-sectional, diagnostic (phase I) multicenter study. No patients had any overt neurological deficits; all underwent venous and lumbar puncture as well as neuropsychological testing. In untreated early-stage patients, cerebrospinal fluid (CSF) viral load correlated with inflammatory parameters, but not significantly with neuropsychological abnormalities. CSF viral load and inflammatory reactions were suppressed in HAART-treated early-stage patients. In HAART-treated late-stage patients, there was a weak correlation between CSF viral load and CSF cell count as well as a moderate correlation with immune activation markers and with distinct cerebral deficits independent of CSF viral load. Seventeen of the 109 patients had higher CSF than plasma viral loads and marked inflammatory reactions and immune activation. In patients with greater plasma than CSF viral loads, the factors contributing to cerebral deficits still need to be identified. The results suggest not only that there is an early "set point" for CSF/central nervous system (CNS) infection, but also that there is a subgroup of patients in whom intrathecal viral replication correlates with cerebral deficits. Lumbar puncture should be performed in all positive patients to identify members of this subgroup and to ascertain what characteristic factors they have in common in order to improve therapy.
本研究的目的是明确在人类免疫缺陷病毒(HIV)感染中,根据脑脊液(CSF)中活跃的病毒复制所定义的中枢神经系统(CNS)感染是否存在关键阶段。109例处于疾病早期和晚期、接受或未接受高效抗逆转录病毒治疗(HAART)的HIV-1阳性同性恋和双性恋患者纳入了这项横断面诊断性(I期)多中心研究。所有患者均无明显神经功能缺损;全部接受了静脉穿刺、腰椎腰椎穿刺以及神经心理学测试。在未接受治疗的早期患者中,脑脊液(CSF)病毒载量与炎症参数相关,但与神经心理学异常无显著相关性。接受HAART治疗的早期患者的脑脊液病毒载量和炎症反应受到抑制。在接受HAART治疗的晚期患者中,脑脊液病毒载量与脑脊液细胞计数之间存在弱相关性,与免疫激活标志物以及与独立于脑脊液病毒载量的明显脑功能缺损存在中度相关性。109例患者中有17例脑脊液病毒载量高于血浆病毒载量,并伴有明显的炎症反应和免疫激活。在血浆病毒载量高于脑脊液病毒载量的患者中,导致脑功能缺损的因素仍有待确定。结果表明,不仅脑脊液/中枢神经系统(CNS)感染存在早期“设定点”,而且存在一个鞘内病毒复制与脑功能缺损相关的患者亚组。所有阳性患者均应进行腰椎穿刺,以识别该亚组的成员,并确定他们共有的特征性因素,以便改善治疗。