He Yihui, Liu Hao, Ren Meixin, Sun Gaungqiang, Ma Yundong, Cai Miaotian, Wang Rui, Wang Lei, Zhang Tong, Zhang Yang
Postgraduate Union Training Base of Jinzhou Medical University, PLA Rocket Force Characteristic Medical Center, Beijing, China.
Department of Neurology, PLA Rocket Force Characteristic Medical Center, Beijing, China.
Front Immunol. 2025 Mar 19;16:1436589. doi: 10.3389/fimmu.2025.1436589. eCollection 2025.
In the realm of public health, late human immunodeficiency virus (HIV) diagnosis remains prevalent and is associated with neuropsychiatric adverse events. However, there is limited documentation regarding the impact of late HIV diagnosis (LD) on brain integrity, neurotrophic factors, endocrine function, and immunity in HIV-positive men who have sex with men (MSM).
Participants (38 LD and 34 non-LD of MSM) underwent comprehensive infectious disease and psychiatric assessments, multimodal magnetic resonance imaging (MRI) scans, neurotrophic factors, endocrine, and immunological evaluations. Immune cell levels, along with peripheral plasma concentrations of neurotrophic factors and hormones, were measured using enzyme-linked immunosorbent assays and flow cytometry, respectively. T1-weighted images along with resting-state functional MRI were applied to assess brain function and structure while also examining correlations between imaging alterations and clinical as well as peripheral blood variables. The data for this study originated from a subset of the cohort in HIV-associated neuropsychiatric disorders research.
Compared to participants in the non-LD group, those in the LD group showed a lower total gray matter volume (GMV), with reduced GMV primarily observed in the left supramarginal gyrus. Participants in the LD group exhibited differences in brain function with certain regions and decreased functional connectivity between these altered regions and connected structures. A two-way factorial analysis of variance examining the main effects and interactions between groups and neuropsychiatric disorders revealed significant main effects of LD on specific brain regions. Furthermore, we found that individuals in the LD group had higher levels of cortisol, a lower frequency of central memory T cells, and elevated expression levels of perforin in double-negative T cells. These imaging findings were significantly correlated with endocrine, immune, and clinical variables.
This study suggests that LD may contribute to brain injury, endocrine disruption, and immune dysregulation in HIV-positive MSM. Consequently, there is an urgent need to develop public health strategies targeting late diagnosis, with a focus on strengthening screening and early detection for high-risk populations, as well as monitoring brain injury, endocrine, and immune functions in individuals with LD, and formulating precise, individualized intervention strategies to reduce the long-term impact of LD on the health of HIV-positive MSM.
在公共卫生领域，人类免疫缺陷病毒（HIV）晚期诊断仍然普遍存在，并且与神经精神不良事件相关。然而，关于HIV晚期诊断（LD）对男男性行为者（MSM）中HIV阳性者的脑完整性、神经营养因子、内分泌功能和免疫的影响，相关文献有限。
参与者（38名LD的MSM和34名非LD的MSM）接受了全面的传染病和精神病学评估、多模态磁共振成像（MRI）扫描、神经营养因子、内分泌和免疫学评估。免疫细胞水平以及神经营养因子和激素的外周血浆浓度分别使用酶联免疫吸附测定法和流式细胞术进行测量。应用T1加权图像以及静息态功能MRI来评估脑功能和结构，同时检查成像改变与临床以及外周血变量之间的相关性。本研究的数据源自HIV相关神经精神疾病研究队列的一个子集。
与非LD组的参与者相比，LD组的参与者总灰质体积（GMV）较低，主要在左侧缘上回观察到GMV减少。LD组的参与者在脑功能方面存在差异，某些区域以及这些改变区域与相连结构之间的功能连接减少。一项双向方差分析，检验组间和神经精神疾病之间的主效应和相互作用，结果显示LD对特定脑区有显著的主效应。此外，我们发现LD组的个体皮质醇水平较高、中枢记忆T细胞频率较低以及双阴性T细胞中穿孔素的表达水平升高。这些成像结果与内分泌、免疫和临床变量显著相关。
本研究表明，LD可能导致HIV阳性MSM出现脑损伤、内分泌紊乱和免疫失调。因此，迫切需要制定针对晚期诊断的公共卫生策略，重点是加强对高危人群的筛查和早期检测，以及监测LD个体的脑损伤、内分泌和免疫功能，并制定精确的个体化干预策略，以减少LD对HIV阳性MSM健康的长期影响。
