Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey.
Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
JAMA Netw Open. 2021 Jan 4;4(1):e2031190. doi: 10.1001/jamanetworkopen.2020.31190.
Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date.
To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019.
Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status.
After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P < .001) and thalamic (mean [SE] β = 32.24 [8.96] mm3 per 100 cells/mm3; P < .001) volumes and larger ventricles (mean [SE] β = -391.50 [122.58] mm3 per 100 cells/mm3; P = .001); in participants not taking cART, however, lower current CD4+ cell counts were associated with smaller putamen volumes (mean [SE] β = 57.34 [18.78] mm3 per 100 cells/mm3; P = .003). A dVL was associated with smaller hippocampal volumes (d = -0.17; P = .005); in participants taking cART, dVL was also associated with smaller amygdala volumes (d = -0.23; P = .004).
In a large-scale international population of HIV-positive individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Our findings extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era.
尽管更广泛地可获得联合抗逆转录病毒疗法 (cART)，但 HIV-1 感染仍然是一个全球性的公共卫生挑战。即使在慢性 HIV 感染的治疗患者中，神经认知障碍也常常持续存在，影响生活质量。确定与体内感染相关的神经解剖途径可能可以阐明这些缺陷背后的神经病理过程。然而，发表的神经影像学研究结果来自相对较小、异质的队列，结果不一致，限制了迄今为止得出的结论的普遍性。
检查与 HIV 负担最常收集的临床评估（CD4+ T 细胞计数和病毒载量）相关的结构性脑关联，这些评估在全球范围内具有不同人口统计学和临床特征的 HIV 感染者中具有可推广性。
设计、地点和参与者：本横断面研究在通过荟萃分析增强神经影像学遗传学 (ENIGMA) 联盟内建立了 HIV 工作组，以汇集和协调来自世界各地 HIV 神经影像学研究的现有数据。共有 13 项研究的 1295 名 HIV 阳性成年人的数据来自非洲、亚洲、澳大利亚、欧洲和北美。从 2014 年 11 月 1 日至 2019 年 12 月 31 日，随着研究的加入，数据从数据集中提取区域和全脑分割。
从 T1 加权磁共振图像中提取 8 个皮质下脑区的体积估计值，以确定与 HIV 阳性参与者当前免疫抑制的血浆标志物（CD4+ T 细胞计数）或可检测的血浆病毒载量（dVL）的关联。事后敏感性分析按 cART 状态对数据进行分层。
经过质量保证后，仍有 1203 名 HIV 阳性个体的数据（平均[标准差]年龄，45.7[11.5]岁；880[73.2%]男性；897[74.6%]接受 cART）。当前 CD4+ 细胞计数较低与海马体（平均[SE]β=16.66[4.72]mm3/每 100 个细胞/mm3；P<0.001）和丘脑（平均[SE]β=32.24[8.96]mm3/每 100 个细胞/mm3；P<0.001）体积减小和脑室增大（平均[SE]β=-391.50[122.58]mm3/每 100 个细胞/mm3；P=0.001）相关；然而，在未服用 cART 的参与者中，当前 CD4+ 细胞计数较低与壳核体积较小（平均[SE]β=57.34[18.78]mm3/每 100 个细胞/mm3；P=0.003）相关。dVL 与海马体体积较小（d=-0.17；P=0.005）相关；在服用 cART 的参与者中，dVL 还与杏仁核体积较小（d=-0.23；P=0.004）相关。
在一个大规模的国际 HIV 阳性人群中，结构的体积结构与当前的血浆标志物一致。我们的发现超越了经典的基底节区域，可能代表了 cART 时代 HIV 感染的可推广的大脑特征。
