NEUROLOGICAL RESPONSE TO HAART

有证据表明，高效抗逆转录病毒疗法（HAART）改善了艾滋病毒感染者的生活质量和数量。越来越多但尚未得到充分证实的证据表明，高效抗逆转录病毒疗法对艾滋病毒感染的神经系统并发症也有显著的有益效果。关于这种神经系统改善的确切机制的信息很少。我们建议对一组HIV感染（HIV+）受试者进行评估，这些受试者要么是HAART新手，要么是HAART治疗失败，因为系统病毒负担增加，他们将切换到另一种治疗方案。他们将在开始或改变HAART之前对神经系统功能进行深入评估，然后进行纵向随访，以评估神经系统功能随时间的变化。我们的前提是，在HAART治疗下，神经系统功能将随着全身和脑脊液病毒载量的减少而改善。我们认为，这种改善将是由于神经系统中促炎细胞因子/趋化因子的下调，这将通过脑脊液中这些化合物的减少来证明。通过评估血浆和脑脊液HIV RNA病毒载量、神经心理学、神经学和心理学，包括生活质量和依从性，对受试者进行临床特征分析。我们将通过基因分型、共受体类型（CXCR4、CCR5）、合胞/非合胞诱导来完成病毒的特征，并评估脑脊液和血浆中病毒的这些差异。我们将评估趋化因子（MCP-1, MIP- 1alpha, SDF-1alpha），中枢神经系统炎症标志物（TNFalpha, IL-6），并测定神经毒性（神经元培养中的钙内流成像和细胞死亡）。为了进一步确定HAART治疗失败后对全身和中枢神经系统病毒载量的相对影响，我们将描述和比较脑脊液和血浆室中的病毒群。

The evidence is clear that highly active antiretroviral therapy (HAART) improves quality and quantity of life in HIV infected patients. There is growing but as yet poorly substantiated evidence that HAART also has a marked beneficial effect on the nervous system complications of HIV infection. There is little information on the exact mechanism of this nervous system improvement. We propose to evaluate a group of HIV infected (HIV+) subjects who are either HAART naive or have failed one regimen of HAART as indicated by an increase in systemic viral burden, and who are to be switched to another regimen. They will have indepth evaluation of nervous system function before starting or changing HAART, and then will be followed longitudinally to assess changes in nervous system function over time. Our premise is that, with HAART, nervous system function will improve in association with reduction of systemic and CSF viral load. We believe the improvement will be due to a down regulation of proinflammatory cytokine/chemokines in the nervous system, and this will be evidenced by a reduction in these compounds in the cerebrospinal fluid. Subjects will be clinically characterized through assessment of plasma and CSF HIV RNA viral load, neuropsychological, neurological, and psychological, including quality of life and adherence. We will complete viral characterization through genotyping, co-receptor type (CXCR4, CCR5), syncytia/nonsyncytial induction and assess these differences between virus in CSF and plasma. We will assess chemokines (MCP-1, MIP- 1alpha, SDF-1alpha), CNS inflammatory markers (TNFalpha, IL-6), and assay neurotoxicity (calcium influx imaging and cell death in neuronal cultures). To further aid in the determination of the relative effects of HAART on systemic and CNS viral load with failure, we will characterize and compare the virus populations in the CSF and plasma compartments.