抗逆转录病毒治疗相关的HIV感染者脑功能动态改变

doi:10.11938/cjmr20253175

波谱学杂志 ›› 2026, Vol. 43 ›› Issue (1): 61-70.doi: 10.11938/cjmr20253175cstr: 32225.14.cjmr20253175

抗逆转录病毒治疗相关的HIV感染者脑功能动态改变

王奕雯¹^,⁵, 吴光耀²^,³^,^#(), 文之²^,⁴, 林富春¹^,⁵^,^*()

1.磁共振波谱与成像全国重点实验室，武汉国家磁共振中心，中国科学院精密测量科学与技术创新研究院，湖北武汉 430071
2.武汉大学中南医院放射科，湖北武汉 430071
3.深圳大学总医院放射科，广东深圳 518055
4.武汉大学人民医院放射科，湖北武汉 430060
5.中国科学院大学，北京 100049

收稿日期:2025-07-14 出版日期:2026-03-05 在线发表日期:2025-08-28
通讯作者: #Tel: 0755-21838287, E-mail: wuguangy2002@163.com;*Tel: 027-87198687, E-mail: fclin@wipm.ac.cn.
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

WANG Yiwen¹^,⁵, WU Guangyao²^,³^,^#(), WEN Zhi²^,⁴, LIN Fuchun¹^,⁵^,^*()

1. State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China
2. Department of Radiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
3. Department of Radiology, Shenzhen University General Hospital, Shenzhen 518055, China
4. Department of Radiology, Renmin Hospital, Wuhan University, Wuhan 430060, China
5. University of Chinese Academy of Sciences, Beijing 100049, China

Received:2025-07-14 Published:2026-03-05 Online:2025-08-28
Contact: #Tel: 0755-21838287, E-mail: wuguangy2002@163.com;*Tel: 027-87198687, E-mail: fclin@wipm.ac.cn.

摘要/Abstract

摘要：

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．

关键词: 人类免疫缺陷病毒, 抗逆转录病毒治疗, 功能磁共振成像, 动态功能连接

Abstract:

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.

Key words: HIV, antiretroviral therapy (ART), functional magnetic resonance imaging (fMRI), dynamic functional connectivity (dFC)

中图分类号:

O482.53

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.

WANG Yiwen, WU Guangyao, WEN Zhi, LIN Fuchun. Antiretroviral Therapy-related Alteration of Brain Functional Dynamics in People with HIV[J]. Chinese Journal of Magnetic Resonance, 2026, 43(1): 61-70.

图/表 5

表1

图1

图2

图3

图4

参考文献 36

[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. doi: 10.1371/journal.pone.0240880
[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. doi: 10.1017/S1041610221000156
[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. doi: S0166-2236(20)30149-1 pmid: 32682564
[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. doi: 10.1038/s41598-017-03446-w pmid: 28646196
[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. doi: 10.11938/cjmr20243129
[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. doi: 10.3174/ajnr.A5432
[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. doi: 10.1097/QAD.0000000000000151 pmid: 24300546
[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. doi: 10.1093/scan/nsaa114
[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. doi: 10.11938/cjmr20243102
[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. doi: 10.1111/cns.v26.9
[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. doi: 10.1093/brain/awx233
[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. doi: 10.1073/pnas.1216856110 pmid: 23440216
[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. doi: 10.1002/hbm.1048 pmid: 11559959
[15]	HUTCHISON R M, WOMELSDORF T, ALLEN E A, et al. Dynamic functional connectivity: Promise, issues, and interpretations[J]. NeuroImage, 2013, 80:360-378. doi: 10.1016/j.neuroimage.2013.05.079 pmid: 23707587
[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. doi: 10.1097/QAI.0b013e318249db17 pmid: 22269799
[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. doi: 10.1007/s13365-019-00723-4 pmid: 30767174
[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. doi: 10.1007/s13365-020-00865-w pmid: 32572834
[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. doi: 10.1097/QAD.0000000000003759
[20]	ZHUANG Y, QIU X, WANG L, et al. Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals[J]. J Neurovirol, 2017, 23(5): 704-712. doi: 10.1007/s13365-017-0553-9 pmid: 28791662
[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. doi: 10.1002/hbm.v42.1
[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. doi: 10.1097/QAD.0000000000000611 pmid: 25849834
[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. doi: 10.1016/j.brainresbull.2025.111231
[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. doi: 10.1186/s12879-024-10397-x pmid: 39780061
[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. doi: 10.1007/s11481-015-9634-9
[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. doi: 10.1016/j.neuroimage.2007.07.007 pmid: 17761438
[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. doi: 10.1162/neco.1995.7.6.1129 pmid: 7584893
[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. doi: 10.3389/fnsys.2011.00002 pmid: 21442040
[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. doi: 10.1093/cercor/bhs352 pmid: 23146964
[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. doi: 10.1002/mrm.1910350312 pmid: 8699946
[32]	ZALESKY A, FORNITO A, BULLMORE E T. Network-based statistic: Identifying differences in brain networks[J]. NeuroImage, 2010, 53(4): 1197-1207. doi: 10.1016/j.neuroimage.2010.06.041 pmid: 20600983
[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. doi: 10.3389/fnhum.2015.00386 pmid: 26175682
[34]	THOMAS J B, BRIER M R, SNYDER A Z, et al. Pathways to neurodegeneration[J]. Neurology, 2013, 80(13): 1186-1193. doi: 10.1212/WNL.0b013e318288792b
[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. doi: 10.1007/s11065-020-09465-1 pmid: 33515170

	未治疗组	ART治疗组	健康对照组	P值
受试者人数	56	45	68	NA
年龄/岁	41.07±11.36	45.38±10.46	43.34±15.16	0.22^a
性别（男/女）	42/14	25/20	41/27	0.09^b
Mean FD/ mm	0.10±0.07	0.09±0.07	0.09±0.05	0.40^a
诊断时间/月	4.45±12.94	53.11±35.89	NA	<0.001^c
治疗时间/月	NA	41.51±31.70	NA	NA
CD4计数/(cells/mm³)	116.11±137.67	377.05±205.93	NA	<0.001^c
MoCA评分	23.02±5.53	23.40±4.63	NA	0.99^c

抗逆转录病毒治疗相关的HIV感染者脑功能动态改变

Antiretroviral Therapy-related Alteration of Brain Functional Dynamics in People with HIV

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 36

相关文章 12

编辑推荐

Metrics

本文评价

[1]	陈琪, 李海东, 方媛, 沈路阳, 刘无己, 罗明, 李业成, 张鸣, 赵修超, 石磊, 周倩, 韩叶清, 周欣. ¹²⁹Xe通气功能MRI与肺部病灶类型关联研究[J]. 波谱学杂志, 2024, 41(3): 276-285.
[2]	邱先鑫,韩旭,汪耀,丁伟娜,孙雅文,周滟,雷皓,林富春. 网络游戏障碍人群大脑功能网络rich club结构的改变[J]. 波谱学杂志, 2022, 39(3): 258-266.
[3]	崔阳阳,梁怀彬,朱千,汤伟,高婷婷,刘建仁,杜小霞. 结合局部一致性和低频振幅探究躯体症状障碍患者大脑自发性活动的改变[J]. 波谱学杂志, 2022, 39(1): 64-71.
[4]	胡颖,王丽嘉,聂生东. 融合t-分布随机邻域嵌入与自动谱聚类的脑功能精细分区方法[J]. 波谱学杂志, 2021, 38(3): 392-402.
[5]	贾嘉莹, 况立群, 熊风光, 韩燮. 基于持久同调的复杂脑网络动态演化分析[J]. 波谱学杂志, 2021, 38(1): 80-91.
[6]	辛红涛, 吴光耀, 文之, 雷皓, 林富春. 抗逆转录病毒治疗对艾滋病患者脑灰质体积的影响[J]. 波谱学杂志, 2021, 38(1): 69-79.
[7]	程力维, 王璐璐, 钟凯. fMRI在经颅直流电刺激研究中的应用进展[J]. 波谱学杂志, 2020, 37(4): 533-546.
[8]	刘伟, 王慧, 王二磊, 陈光强, 杨晓冬. 一种用于fMRI的嗅觉刺激装置优化与验证[J]. 波谱学杂志, 2017, 34(4): 519-527.
[9]	董涛, 梁思, 王慧, 杨晓冬. 一种用于fMRI的温度觉刺激装置的设计与验证[J]. 波谱学杂志, 2016, 33(1): 54-65.
[10]	王骁冠1–3，王慧3，常严3，徐雅洁3，张广才3，蒋瑞瑞1–3，杨晓冬3*. 一种用于 fMRI 的嗅觉刺激装置设计与验证[J]. 波谱学杂志, 2014, 31(4): 477-487.
[11]	杨丽琴, 林富春, 雷皓. 静息状态下脑功能连接的磁共振成像研究[J]. 波谱学杂志, 2010, 27(3): 326-340.
[12]	杨萍1,2 ; 王金星1 ; 晁月盛1 . 增强低场下脑功能磁共振成像显著性的研究[J]. 波谱学杂志, 2009, 26(2): 247-254.