Department of Psychiatry and The Behavioral Sciences, University of Southern California Keck School of Medicine, Los Angeles, CA.
Centre for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
AIDS. 2021 Jul 15;35(9):1375-1384. doi: 10.1097/QAD.0000000000002862.
We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART).
Longitudinal retrospective cohort study of children with controlled blood HIV replication.
Children (N = 213; 57% girls) started ART at less than 3 years of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11 years, and achieved controlled viremia (HIV-1 RNA <400 copies/ml for ≥9 months before initial assessment). Twenty-three plasma biomarkers were measured at onset of controlled viremia, week 0 (first neurodevelopmental assessment), and week 48 (second neurodevelopmental assessment). Factor analysis was conducted at each time point. Multivariable linear regressions assessed associations between factors and neurodevelopmental scores.
Median age at week 0 was 7.0 years. Eighteen biomarkers loaded on six factors: a (L-10, IFNγ, IFNα2, IL-1β, IL-6, IP-10, TNFα); B (sCD163, sICAM-1, sVCAM-1, CRP); C (sE-selectin, sP-selectin); D [MIP-1β, vascular endothelial growth factor (VEGF)-A]; E (sCD14, CRP); and F (CX3CL1, MCP-1). Higher factor B scores were consistently associated with worse cognition and attention/impulsivity, and higher factor D scores with better attention/impulsivity.
These results suggest a detrimental effect of increased endothelial cell activation (sICAM-1, sVCAM-1) and monocyte/macrophage scavenger function (sCD163) and a beneficial effect of increased CCR5 ligand and HIV entry blocker MIP-1β and angiogenesis stimulant-VEGF concentrations on the neurodevelopment of children with PHIV. The model that emerges is of vascular inflammation leading to neurodevelopmental deficits. The role of persistent HIV replication in the central nervous system also needs to be further explored.
我们研究了在抗逆转录病毒治疗（ART）下，血 HIV 得到控制的撒哈拉以南非洲儿童中，血浆生物标志物与神经发育之间的关系。
对血 HIV 复制得到控制的儿童进行纵向回顾性队列研究。
儿童（N=213；57%为女孩）在 3 岁以下开始接受 ART，在 5-11 岁时进行神经发育评估（认知、注意力/冲动性、运动能力、整体执行功能），并在初始评估前至少 9 个月实现血 HIV 得到控制（HIV-1 RNA <400 拷贝/ml）。在开始控制病毒血症时（第 0 周）、第 0 周（首次神经发育评估）和第 48 周（第二次神经发育评估），测量了 23 种血浆生物标志物。在每个时间点进行因子分析。多元线性回归评估因子与神经发育评分之间的关系。
第 0 周时的中位年龄为 7.0 岁。有 18 种生物标志物可加载到六个因子上：A（L-10、IFNγ、IFNα2、IL-1β、IL-6、IP-10、TNFα）；B（sCD163、sICAM-1、sVCAM-1、CRP）；C（sE-选择素、sP-选择素）；D [MIP-1β、血管内皮生长因子（VEGF）-A]；E（sCD14、CRP）；F（CX3CL1、MCP-1）。因子 B 评分越高，认知和注意力/冲动性越差，因子 D 评分越高，注意力/冲动性越好。
这些结果表明，内皮细胞激活（sICAM-1、sVCAM-1）和单核细胞/巨噬细胞清除功能（sCD163）增加，以及 CCR5 配体和 HIV 进入抑制剂 MIP-1β 和血管生成刺激物 VEGF 浓度增加对 PHIV 儿童的神经发育产生有害影响。出现的模型是血管炎症导致神经发育缺陷。中枢神经系统中持续 HIV 复制的作用也需要进一步探索。
