Hawaii Center for AIDS, Department of Medicine, University of Hawaii, Honolulu, 96816, USA.
Cereb Cortex. 2012 Sep;22(9):2065-75. doi: 10.1093/cercor/bhr285. Epub 2011 Oct 19.
High levels of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs), and specifically within CD14+ blood monocytes, have been found in HIV-infected individuals with neurocognitive impairment and dementia. The failure of highly active antiretroviral therapy (HAART) to eliminate cognitive dysfunction in HIV may be secondary to persistence of HIV-infected PBMCs which cross the blood-brain barrier, leading to perivascular inflammation and neuronal injury. This study assessed brain cortical thickness relative to HIV DNA levels and identified, we believe for the first time, a neuroimaging correlate of detectable PBMC HIV DNA in subjects with undetectable HIV RNA. Cortical thickness was compared between age- and education-matched groups of older (>40 years) HIV-seropositive subjects on HAART who had detectable (N = 9) and undetectable (N = 10) PBMC HIV DNA. Statistical testing revealed highly significant (P < 0.001) cortical thinning associated with detectable HIV DNA. The largest regions affected were in bilateral insula, orbitofrontal and temporal cortices, right superior frontal cortex, and right caudal anterior cingulate. Cortical thinning correlated significantly with a measure of psychomotor speed. The areas of reduced cortical thickness are key nodes in cognitive and emotional processing networks and may be etiologically important in HIV-related neurological deficits.
外周血单个核细胞（PBMC）中高水平的人类免疫缺陷病毒（HIV）DNA，特别是在 CD14+血液单核细胞中，已在患有神经认知障碍和痴呆的 HIV 感染者中发现。高效抗逆转录病毒疗法（HAART）未能消除 HIV 感染者的认知功能障碍，可能是由于 HIV 感染的 PBMC 持续存在，这些 PBMC 穿过血脑屏障，导致血管周围炎症和神经元损伤。本研究评估了大脑皮质厚度与 HIV DNA 水平的关系，并首次确定了在 HIV RNA 不可检测的情况下，可检测到 PBMC HIV DNA 的神经影像学相关性。我们比较了年龄和教育相匹配的接受 HAART 的年长（>40 岁）HIV 阳性受试者中，可检测到（N=9）和不可检测到（N=10）PBMC HIV DNA 的两组之间的皮质厚度。统计检验显示，与可检测到的 HIV DNA 相关的皮质变薄具有高度显著意义（P<0.001）。受影响最大的区域位于双侧脑岛、眶额和颞叶皮质、右侧额上回和右侧扣带回前部。皮质变薄与心理运动速度的一个衡量标准显著相关。这些皮质厚度降低的区域是认知和情感处理网络的关键节点，可能在 HIV 相关的神经功能缺陷中具有重要的病因学意义。
