Eggers C C, van Lunzen J, Buhk T, Stellbrink H J
Neurologische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):259-64. doi: 10.1097/00042560-199903010-00007.
To assess the kinetics of viral replication and decay in cerebrospinal fluid (CSF), we studied the short-term effects of highly active antiretroviral therapy (HAART) on CSF HIV-1 RNA concentrations. In 15 HIV-positive patients, HIV RNA concentrations were measured in paired CSF and plasma/serum samples. Samples were obtained prior to and 5 to 24 days after initiation or change of HAART. The short-term effects of interruption of HAART were tested in 2 patients. Viral load was measured by the Roche Amplicor assay. During HAART, in 12 of 15 patients a significant reduction of CSF HIV RNA concentration was observed, ranging from 0.55 to 2.77 log10 (median, 1.37 log10). This was paralleled by a reduction of blood viremia ranging from 0.12 to 3.0 log10 (median, 1.65 log10). The median half-life, as calculated from the slopes of the two time-point measurements, for CSF and blood viral load was 2.66 and 2.36 days, respectively. In 2 patients, CSF viral load remained essentially unchanged despite substantial reduction of plasma viral load. In 1 patient, after interruption of HAART, a rapid increase of HIV RNA in the CSF and blood was seen. No correlation was found between the CSF:blood albumin ratio as a measure of the functional integrity of the blood-CSF barrier and the ratio of CSF:blood RNA concentration, which suggests that no major passive influx of HIV RNA moves from the blood into the CSF compartment. However, a correlation existed between the CSF cell count and the CSF viral load (r = 0.74; p < .003). We conclude that, in most HIV-infected individuals, the decay of viral load in the CSF is similarly rapid as that seen in plasma. The rapid kinetics of virus found in the CSF suggest that it may be produced by rapidly proliferating cells, such as lymphocytes.
为评估病毒在脑脊液(CSF)中的复制和衰减动力学,我们研究了高效抗逆转录病毒疗法(HAART)对脑脊液中HIV-1 RNA浓度的短期影响。在15例HIV阳性患者中,对配对的脑脊液和血浆/血清样本中的HIV RNA浓度进行了测量。样本在开始或改变HAART之前以及之后5至24天采集。在2例患者中测试了中断HAART的短期影响。通过罗氏Amplicor检测法测量病毒载量。在HAART期间,15例患者中有12例脑脊液中HIV RNA浓度显著降低,降低幅度为0.55至2.77 log10(中位数为1.37 log10)。同时血液病毒血症也有所降低,降低幅度为0.12至3.0 log10(中位数为1.65 log10)。根据两个时间点测量的斜率计算,脑脊液和血液病毒载量的中位半衰期分别为2.66天和2.36天。在2例患者中,尽管血浆病毒载量大幅降低,但脑脊液病毒载量基本保持不变。在1例患者中,中断HAART后,脑脊液和血液中的HIV RNA迅速增加。作为血脑屏障功能完整性指标的脑脊液:血液白蛋白比值与脑脊液:血液RNA浓度比值之间未发现相关性,这表明没有大量HIV RNA从血液被动流入脑脊液腔室。然而,脑脊液细胞计数与脑脊液病毒载量之间存在相关性(r = 0.74;p <.003)。我们得出结论,在大多数HIV感染个体中,脑脊液中病毒载量的衰减与血浆中一样迅速。脑脊液中发现的病毒快速动力学表明它可能由快速增殖的细胞(如淋巴细胞)产生。