Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
PLoS One. 2013 Jul 31;8(7):e70164. doi: 10.1371/journal.pone.0070164. Print 2013.
Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury.
We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).
The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.
Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.
尽管采用了联合抗逆转录病毒疗法（cART），HIV 仍会导致认知障碍。主要理论认为外周血单核细胞 HIV DNA 库是病毒向大脑传播的机制。尽管采用了 cART，这些储库仍然存在。本研究旨在确定 CD14（+）富集单核细胞中的 HIV DNA 水平是否可预测认知障碍和脑损伤。
我们对 61 名未经 cART 治疗的 HIV 感染泰国人进行了前瞻性研究，并以盲法方式测量了 CD14（+）富集单核细胞样本中的 HIV DNA。我们通过共识小组确定 HAND 诊断，所有参与者均接受磁共振波谱（MRS）以测量脑损伤标志物。通过脑脊液（CSF）中的细胞因子测量免疫激活。
参与者的平均（标准差）年龄为 35（6.9）岁，CD4 淋巴细胞计数为 236（139），对数 10 血浆 HIV RNA 为 4.8（0.73）。61 名参与者中有 28 名符合 HAND 标准。未调整和调整模型均显示 CD14（+）HIV DNA 的对数与 HAND 相关（p=0.001）。HIV DNA 每增加 1 个对数，HAND 的优势比增加 14.5（拷贝数增加 10 倍）。血浆 CD14（+）HIV DNA 与血浆和 CSF 新蝶呤（p=0.023）以及 MRS 多个脑区神经元损伤（N-乙酰天冬氨酸降低）和神经胶质功能障碍（肌醇升高）标志物相关。
未经治疗的 HIV 阳性受试者中，外周血单核细胞（CD14（+））中 HIV DNA 库的储库负担增加了 HAND 的风险，与 CSF 免疫激活以及 MRS 检测到的脑损伤和神经胶质功能障碍直接相关。
