De Luca Andrea, Ciancio B C, Larussa D, Murri R, Cingolani A, Rizzo M G, Giancola M L, Ammassari A, Ortona L
Istituto di Clinica delle Malattie Infettive, Università Cattolica del S Cuore, Largo Francesco Vito, I-00168 Rome, Italy.
Neurology. 2002 Aug 13;59(3):342-7. doi: 10.1212/wnl.59.3.342.
To investigate in detail factors associated with independent replication of HIV-1 in CNS, and to predict its therapeutic control.
HIV RNA concentration was measured by PCR in 134 cross-sectional paired plasma and CSF samples from 95 patients infected with HIV-1 with various conditions, and in longitudinal CSF samples from 50 patients on antiretroviral treatment. Monocyte chemotactic protein (MCP)-1 was quantified in CSF by ELISA.
High HIV RNA levels either in plasma or in CSF did not correlate with HIV RNA concentration in the paired biologic sample. A high CSF-to-plasma HIV RNA ratio, suggesting independent viral replication in the CNS, was associated with higher CSF viral load and higher CSF MCP-1 levels. Higher MCP-1 levels in the CSF were also associated with neurologic disorders and were not influenced by the use of highly active antiretroviral therapy (HAART). A higher number of antiretroviral drugs with CSF penetration correlated with a more profound CSF HIV-1 load reduction, independently from the use of HAART alone. Virologic suppression in CSF was predicted by a higher number of CSF-penetrating antiretrovirals and by the baseline CSF viral load, whereas lower baseline CD4 counts and higher MCP-1 levels were associated with increased risk of virologic failure.
Quantification of HIV RNA in CSF is clinically useful, particularly in patients with neurologic disorders. CSF penetration of antiretrovirals must be considered when choosing treatments, mainly in patients with higher CSF viral loads, advanced disease, and CNS disorders associated with significant macrophage activation.
详细研究与HIV-1在中枢神经系统中独立复制相关的因素，并预测其治疗控制情况。
采用聚合酶链反应（PCR）检测了95例不同病情的HIV-1感染患者的134份横断面配对血浆和脑脊液样本中的HIV RNA浓度，以及50例接受抗逆转录病毒治疗患者的纵向脑脊液样本中的HIV RNA浓度。通过酶联免疫吸附测定（ELISA）对脑脊液中的单核细胞趋化蛋白（MCP）-1进行定量分析。
血浆或脑脊液中高HIV RNA水平与配对生物样本中的HIV RNA浓度无关。脑脊液与血浆中HIV RNA比值较高，提示中枢神经系统中存在独立的病毒复制，这与较高的脑脊液病毒载量和较高的脑脊液MCP-1水平相关。脑脊液中较高的MCP-1水平也与神经系统疾病相关，且不受高效抗逆转录病毒治疗（HAART）使用的影响。脑脊液穿透性抗逆转录病毒药物数量越多，脑脊液中HIV-1载量降低越显著，且独立于单独使用HAART的情况。脑脊液中的病毒学抑制可通过较多的脑脊液穿透性抗逆转录病毒药物数量和基线脑脊液病毒载量来预测，而较低的基线CD4细胞计数和较高的MCP-1水平与病毒学失败风险增加相关。
脑脊液中HIV RNA的定量分析在临床上具有重要意义，尤其是对于患有神经系统疾病的患者。选择治疗方案时必须考虑抗逆转录病毒药物的脑脊液穿透性，主要针对脑脊液病毒载量较高、疾病进展期以及与显著巨噬细胞活化相关的中枢神经系统疾病患者。
