Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
PLoS One. 2021 May 13;16(5):e0250987. doi: 10.1371/journal.pone.0250987. eCollection 2021.
To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control.
This is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau.
HIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200-350 blood CD4+ T cells/μL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.
应用一组脑脊液（CSF）炎症生物标志物对代表广泛的全身性 HIV-1 免疫抑制、中枢神经系统损伤和病毒控制的分组受试者，描述 HIV-1 感染中中枢神经系统炎症的演变。
这是对存档 CSF 和血液样本的横断面分析，通过免疫测定评估 143 名 HIV-1 感染受试者（分为 8 组）中 10 种功能不同的可溶性炎症生物标志物的浓度：未经治疗的原发性 HIV-1 感染（PHI）；根据其血液 CD4+T 淋巴细胞计数定义的四个未经治疗的组；出现亚急性 HIV 相关痴呆（HAD）的未经治疗患者；接受至少 1 年血浆病毒抑制的抗逆转录病毒治疗的受试者；以及未经治疗的精英控制者。纳入 20 名 HIV-1 未感染对照进行比较。背景生物标志物包括血液 CD4+和 CD8+T 淋巴细胞、CSF 和血液 HIV-1 RNA、CSF 白细胞（WBC）计数、CSF/血液白蛋白比值、CSF 神经丝轻链（NfL）和 CSF t-tau。
HIV-1 感染与广泛的中枢神经系统炎症反应有关，该反应在其病程早期发生，并随着全身疾病进展、神经损伤发展和病毒抑制而变化。未经治疗的个体中，在没有明显 HAD 的情况下，CSF 炎症表现出至少两种随着血液 CD4+T 淋巴细胞减少而出现的总体炎症模式：一种在血液 CD4+T 细胞为 200-350/μL 时达到峰值，与淋巴细胞性 CSF 炎症和 HIV-1 RNA 浓度相关；另一种随着 CD4+T 细胞的全范围下降而逐渐增加，与巨噬细胞反应和中枢神经系统损伤增加相关。亚急性 HAD 的特点是第三种炎症谱，表现为血脑屏障通透性增加，以及强烈的淋巴细胞和巨噬细胞 CSF 炎症。抗逆转录病毒治疗和精英病毒控制抑制 CSF 和血液 HIV-1 感染与 CSF 炎症减少相关，但尚未完全恢复到 HIV-1 血清阴性对照的水平。
