Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources
Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources
复制标题
DOI：
10.1212/wnl.54.4.927
复制
发表时间：
2000-02-22
期刊：
影响因子：
9.9
通讯作者：
McCutchan, JA
中科院分区：
文献类型：
--
作者：
Ellis, RJ;Gamst, AC;McCutchan, JA
目的：通过模拟治疗相关的HIV动力学，确定CSF中HIV病毒的来源。背景：我们假设一个无细胞脑脊液病毒粒子来源于两个主要来源的模型，即系统性非中枢神经系统和中枢神经系统组织，后者包括脑实质和脑膜。该模型预测，随着抗逆转录病毒治疗的开始，脑脊液HIV RNA水平的急性期下降将由优势病毒粒子源（系统与中枢神经系统）的动力学控制。基于先前的观察，我们假设脑脊液病毒粒子的主要来源将在更晚期的疾病中从全身转移到中枢神经系统。方法：分三组进行研究：第一组（n = 5）：无痴呆，早期HIV疾病（CD4（+）淋巴细胞≥400/ μ L）或多细胞血症（CSF白细胞≥4/ μ L）；2组（n = 5）：无痴呆，伴HIV晚期疾病(CD4(+) (400/ μ L)，无多细胞增多；第三组（n = 2）： hiv相关痴呆（HAD）患者。所有患者都开始了新的高效抗逆转录病毒治疗方案，并接受了一系列腰椎穿刺和静脉切开术。结果：2组患者脑脊液HIV RNA的下降速度低于血浆（p < 0.00001）。对于第1组，脑脊液下降率与血浆无显著差异（p < 0.05）。HAD患者在治疗5 - 6周后，血浆HIV RNA下降100倍，但脑脊液HIV RNA升高。结论：在晚期HIV疾病中，脑脊液和血浆HIV动力学变得越来越独立，且在HAD中室间差异最大。我们的研究结果表明，中枢神经系统组织中的病毒复制可能是CSF HIV RNA的主要、独立来源。在HAD患者中，脑实质本身可能是主要的中枢神经系统组织来源，可能需要中枢神经系统靶向治疗策略来根除这种感染。
Objective: To identify the sources of HIV virions in CSF by modeling treatment-associated HIV dynamics. Background: We postulated a model in which cell-free CSF virions originate from two major sources, namely, systemic non-CNS and CNS tissues, the latter including brain parenchyma and meninges. The model predicted that with initiation of antiretroviral therapy, the acute-phase decline in CSF HIV RNA levels would be controlled by the kinetics of the dominant virion source (systemic versus CNS). Based on prior observations, we hypothesized that the dominant source of CSF virions would shift from systemic to CNS in more advanced disease. Methods: Three patient groups were studied: Group 1 (n = 5): nondemented, with early HIV disease (CD4(+) lymphocytes greater than or equal to 400/mu L) or pleocytosis (CSF leukocytes greater than or equal to 4/mu L); Group 2 (n = 5): nondemented, with advanced HIV disease (CD4(+) ( 400/mu L) and no pleocytosis; Group 3 (n = 2): patients with HIV-associated dementia (HAD). All patients began a new, highly active antiretroviral treatment regimen and underwent serial lumbar punctures and phlebotomies. Results: For patients in Group 2, the rate of decline in CSF HIV RNA was slower than in plasma (p < 0.00001). For Group 1, the rate of decline in CSF was not different from plasma (p > 0.25). Patients with HAD showed high CSF HIV RNA after 5 to 6 weeks of treatment despite a 100-fold decrease in plasma HIV RNA, Conclusions: CSF and plasma HIV dynamics became increasingly independent in advanced HIV disease, and the compartmental discrepancy was largest in HAD. Our findings suggest that viral replication in CNS tissues may constitute a major, independent source of CSF HIV RNA. In patients with HAD, brain parenchyma itself may be the principal CNS tissue source, and CNS-targeted treatment strategies may be required to eradicate this infection.