抗逆转录病毒治疗相关的HIV感染者脑功能动态改变
收稿日期: 2025-07-14
网络出版日期: 2025-08-28
基金资助
国家自然科学基金资助项目(82472060);中国科学院前沿科学重大突破项目(QYZDB-SSW-SLH046)
Antiretroviral Therapy-related Alteration of Brain Functional Dynamics in People with HIV
Received date: 2025-07-14
Online published: 2025-08-28
为了调查与抗逆转录病毒治疗（antiretroviral therapy，ART）相关的静息状态功能连接的动态特性，从45名接受治疗的HIV感染者（people with HIV，PWH）、56名未接受治疗的PWH与68名健康对照者采集得到功能磁共振成像数据．使用组独立成分分析、滑动窗分析提取窗功能连接矩阵及量化其动态特性．结果表明，基线状态、弱激活状态体现了HIV相关异常动态及ART相关恢复，弱激活状态体现小脑相关连接恢复、壳核相关功能代偿，基线状态体现除视觉网络外的广泛网络连接恢复．视觉相关连接在两种状态中均体现为ART相关的不良反应．这些发现表明小脑、壳核可能是ART相关恢复的敏感生物标志物，视觉网络可作为辅助治疗的目标．
王奕雯 , 吴光耀 , 文之 , 林富春 . 抗逆转录病毒治疗相关的HIV感染者脑功能动态改变[J]. 波谱学杂志, 2026 , 43(1) : 61 -70 . DOI: 10.11938/cjmr20253175
To investigate the dynamic properties of resting-state functional connectivity associated with antiretroviral therapy (ART), functional magnetic resonance imaging data from 45 treated people with HIV (PWH), 56 untreated PWH, and 68 healthy controls were collected. Group independent component analysis and sliding window analysis were conducted to obtain window-functional connectivity matrices, and their dynamic properties were quantified. The results showed that the baseline state and the weakly activated state reflect HIV-related abnormal dynamics and ART-related recovery. The weakly activated state reflected the recovery of cerebellum-related connections and putamen-related functional compensation. The baseline state reflected the recovery of extensive connections except for the visual network. Visual-related connections reflected ART-related adverse reactions in both states. These findings suggest that the cerebellum and putamen may be sensitive biomarkers for ART-related recovery, and the visual network can serve as a target for adjuvant therapy.
| [1] | WOLDAY D, LEGESSE D, KEBEDE Y, et al. Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia[J]. PLoS One, 2020, 15(10): e0240880. |
| [2] | FLATT A, GENTRY T, KELLETT-WRIGHT J, et al. Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania[J]. Int Psychogeriatr, 2023, 35(7): 339-350. |
| [3] | OSBORNE O, PEYRAVIAN N, NAIR M, et al. The Paradox of HIV blood-brain barrier penetrance and antiretroviral drug delivery deficiencies[J]. Trends Neurosci, 2020, 43(9): 695-708. |
| [4] | WU T, ZHANG J, GENG M, et al. Nucleoside reverse transcriptase inhibitors (NRTIs) induce proinflammatory cytokines in the CNS via Wnt5a signaling[J]. Sci Rep, 2017, 7(1): 4117. |
| [5] | CHEN Q, YANG Z J, CHENG X Y, et al. Application of magnetic resonance imaging technology in pediatric exercise intervention research[J]. Chinese J Magn Reson, 2025, 42(2): 195-204. |
| 陈群, 杨子剑, 程心怡, 等. 磁共振成像技术在儿童运动干预研究中的应用[J]. 波谱学杂志, 2025, 42(2): 195-204. | |
| [6] | CONNOR E E, ZEFFIRO T A, ZEFFIRO T A. Brain structural changes following HIV infection: meta-analysis[J]. AJNR Am J Neuroradiol, 2018, 39(1): 54-62. |
| [7] | PLESSIS S D, VINK M, JOSKA J A, et al. HIV infection and the fronto-striatal system: a systematic review and meta-analysis of fMRI studies[J]. AIDS, 2014, 28(6): 803-811. |
| [8] | GORDON E M, NELSON S M. Three types of individual variation in brain networks revealed by single-subject functional connectivity analyses[J]. Curr Opin Behav Sci, 2021, 40:79-86. |
| [9] | IRAJI A, FAGHIRI A, LEWIS N, et al. Tools of the trade: estimating time-varying connectivity patterns from fMRI data[J]. Soc Cogn Affect Neurosci, 2020, 16(8): 849-874. |
| [10] | WANG X, WANG Y, LAN Q. Time-varying analysis of brain networks based on high-order dynamic functional connections in mild cognitive impairment[J]. Chinese J Magn Reson, 2024, 41(3): 286-303. |
| 王霞, 王勇, 兰青. 基于轻度认知障碍高阶动态功能连接的脑网络时变分析[J]. 波谱学杂志, 2024, 41(3): 286-303. | |
| [11] | GU Y, LIN Y, HUANG L, et al. Abnormal dynamic functional connectivity in Alzheimer’s disease[J]. CNS Neurosci Ther, 2020, 26(9): 962-971. |
| [12] | KIM J, CRIAUD M, CHO S S, et al. Abnormal intrinsic brain functional network dynamics in Parkinson’s disease[J]. Brain, 2017, 140(11): 2955-2967. |
| [13] | LIU X, DUYN J H. Time-varying functional network information extracted from brief instances of spontaneous brain activity[J]. Proc Natl Acad Sci USA, 2013, 110(11): 4392-4397. |
| [14] | CALHOUN V D, ADALI T, PEARLSON G D, et al. A method for making group inferences from functional MRI data using independent component analysis[J]. Hum Brain Mapp, 2001, 14(3): 140-151. |
| [15] | HUTCHISON R M, WOMELSDORF T, ALLEN E A, et al. Dynamic functional connectivity: Promise, issues, and interpretations[J]. NeuroImage, 2013, 80:360-378. |
| [16] | ANCES B M, ORTEGA M, VAIDA F, et al. Independent effects of HIV, aging, and HAART on brain volumetric measures[J]. J Acquir Immune Defic Syndr, 2012, 59(5): 469-477. |
| [17] | NIR T M, JAHANSHAD N, CHING C R K, et al. Progressive brain atrophy in chronically infected and treated HIV+ individuals[J]. J Neurovirol, 2019, 25(3): 342-353. |
| [18] | KATO T, YOSHIHARA Y, WATANABE D, et al. Neurocognitive impairment and gray matter volume reduction in HIV-infected patients[J]. J Neurovirol, 2020, 26(4): 590-601. |
| [19] | WANG Y, WU G, WEN Z, et al. Highly active antiretroviral therapy-related effects on morphological connectivity in HIV[J]. AIDS, 2024, 38(2): 207-215. |
| [20] | ZHUANG Y, QIU X, WANG L, et al. Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-na?ve HIV-infected individuals[J]. J Neurovirol, 2017, 23(5): 704-712. |
| [21] | ZHUANG Y, ZHANG Z, TIVARUS M, et al. Whole-brain computational modeling reveals disruption of microscale brain dynamics in HIV infected individuals[J]. Hum Brain Mapp, 2021, 42(1): 95-109. |
| [22] | ORTEGA M, BRIER M R, ANCES B M. Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity[J]. AIDS, 2015, 29(6): 703-712. |
| [23] | ZHANG X, LI Z, JI J, et al. CD8+T cells and monocytes were associated with brain alterations in human immunodeficiency virus-infected individuals with cognitive impairment[J]. Brain Res Bull, 2025, 222: 111231. |
| [24] | HE Y, ZHANG Y, JIANG T, et al. The association between rapid antiretroviral therapy initiation and brain structure and function based on multimodal magnetic resonance imaging in HIV-positive men who have sex with men[J]. BMC Infect Dis, 2025, 25(1): 41. |
| [25] | BRIER M R, WU Q, TANENBAUM A B, et al. Effect of HAART on brain organization and function in HIV-negative subjects[J]. J Neuroimmune Pharmacol, 2015, 10(4): 517-521. |
| [26] | YAN C, ZANG Y. DPARSF: a MATLAB toolbox for "pipeline" data analysis of resting-state fMRI[J]. Front Syst Neurosci, 2010, 4: 13. |
| [27] | ASHBURNER J. A fast diffeomorphic image registration algorithm[J]. NeuroImage, 2007, 38(1): 95-113. |
| [28] | BELL A J, SEJNOWSKI T J. An information-maximization approach to blind separation and blind deconvolution[J]. Neural Comput, 1995, 7(6): 1129-1159. |
| [29] | ALLEN E A, ERHARDT E B, DAMARAJU E, et al. A baseline for the multivariate comparison of resting-state networks[J]. Front Syst Neurosci, 2011, 5: 2. |
| [30] | ALLEN E A, DAMARAJU E, PLIS S M, et al. Tracking whole-brain connectivity dynamics in the resting state[J]. Cereb Cortex, 2014, 24(3): 663-676. |
| [31] | FRISTON K J, WILLIAMS S, HOWARD R, et al. Movement-related effects in fMRI time-series[J]. Magn Reson Med, 1996, 35(3): 346-355. |
| [32] | ZALESKY A, FORNITO A, BULLMORE E T. Network-based statistic: Identifying differences in brain networks[J]. NeuroImage, 2010, 53(4): 1197-1207. |
| [33] | WANG J, WANG X, XIA M, et al. GRETNA: a graph theoretical network analysis toolbox for imaging connectomics[J]. Front Hum Neurosci, 2015, 9: 386. |
| [34] | THOMAS J B, BRIER M R, SNYDER A Z, et al. Pathways to neurodegeneration[J]. Neurology, 2013, 80(13): 1186-1193. |
| [35] | SUDHAKAR P, KEDAR S, BERGER J R. The neuro-ophthalmology of HIV-AIDS review of neurobehavioral HIV medicine[J]. Neurobehav HIV Med, 2012, 4: 99-111. |
| [36] | CLARK S V, SEMMEL E S, ALEKSONIS H A, et al. Cerebellar-subcortical-cortical systems as modulators of cognitive functions[J]. Neuropsychol Rev, 2021, 31(3): 422-446. |
/
| 〈 |
|
〉 |