Longitudinal, multimodal analysis of HIV and ART effects on brain metabolism, structure and connectivity in young children

HIV 和 ART 对幼儿大脑代谢、结构和连接性影响的纵向、多模式分析

• 批准号: 9114662
• 负责人: Bharat Bhusan Biswal
• 金额: $ 14.81万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-22 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9114662
• 关键词: 9 year old; Acquired Immunodeficiency Syndrome; Adult; Age; Biochemical; Biological Markers; Birth; Brain; Brain imaging; Child; Childhood; Chronic; Clinical; Clinical Data; Cognitive; Collaborations; Control Groups; Data; Data Analyses; Data Set; Development; Diffusion; Disease; Early Diagnosis; Exposure to; Fetus; Functional Magnetic Resonance Imaging; Funding; Future; General Hospitals; Graph; HIV; HIV Infections; HIV Seropositivity; HIV antiretroviral; Health; Health Policy; Human; Image Analysis; Imaging Techniques; Infant; Institutes; International; Learning; Lipids; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Massachusetts; Measurement; Measures; Modality; Monitor; Multimodal Imaging; National Institute of Allergy and Infectious Disease; Neuraxis; Neurologic; Neuropsychological Tests; New Jersey; Pathology; Perinatal Exposure; Pharmaceutical Preparations; Population; Pregnant Women; Protocols documentation; Psychological Techniques; Randomized; Research; Research Personnel; Rest; Scanning; South Africa; South African; Staging; Structure; Students; Surveys; Task Performances; Technology; Time; Universities; Visual attention; antiretroviral therapy; arm; authority; base; brain metabolism; cohort; executive function; in utero; in vivo; infancy; longitudinal analysis; mitochondrial dysfunction; neuroimaging; neuropsychological; novel; programs; secondary infection; tool

 DESCRIPTION (provided by applicant): In a recent survey in South Africa, 95% of HIV-positive pregnant women received antiretroviral therapy (ART), and 68% of HIV-exposed infants received ART. Among the estimated 330,000 HIV-infected children in South Africa, 58% receive ART. Research suggests that there are long-term effects associated with in utero exposure to HIV and ART, warranting further study of this burgeoning population of HIV-exposed uninfected (HEU) children. In particular, very little is known about the long-term effects of HIV infection an ART treatment on brain development in pediatric populations, which we will investigate in the proposed study. We have access to an on-going longitudinal neuroimaging study combining several complementary, non-invasive magnetic resonance imaging (MRI) data sets with clinical and neuropsychological measures. The existing study (funded from R21 MH096559 and R01 HD071664) has been following a cohort of children carefully monitored since birth as part of the "Children with HIV early antiretroviral therapy" (CHER) trial (part of Comprehensive International Program for Research in AIDS (CIPRA-SA), sponsored by the Division of AIDS, National Institute of Allergy and Infectious Diseases). At 7 weeks, HIV-infected children were randomly assigned to either one of two early ART arms or to a deferred ART arm. In the cohort, the HIV-uninfected control group includes both HIV-unexposed, uninfected (HUU) and HEU children. At 5 and 7 years, children received clinical, neuropsychological and neuroimaging (structural, diffusion and spectroscopic; resting state functional MRI (RS-FMRI) at 7 years only) assessment. At 9 years (beginning June 2014), the same multimodal imaging and evaluations will be repeated. This project seeks to expand the current neuroimaging measures (under the existing R01) to include MR spectroscopic lactate and lipid concentrations, and to develop new multimodal markers involving brain network connectivity measures. We hypothesize that these additional multimodal biomarkers will be sensitive to the effects of HIV infection, timing and long-term usage of ART, and in utero ART/HIV exposure on brain development. This project extends the existing collaboration between Drs Meintjes (University of Cape Town), Laughton (Stellenbosch University), and van der Kouwe (Massachusetts General Hospital) to include Dr Bharat Biswal from New Jersey Institute of Technology (NJIT) who is a leading authority on RS-FMRI analyses, as well as two UCT-based early stage investigators, Drs Holmes and Taylor.

 描述（申请人提供）：在南非最近的一项调查中，95%的艾滋病毒阳性孕妇接受了抗逆转录病毒治疗（ART），68%的艾滋病毒暴露婴儿接受了ART。在南非估计的330，000名艾滋病毒感染儿童中，58%接受了ART。研究表明，宫内暴露于艾滋病毒和ART会产生长期影响，对这一迅速增长的艾滋病毒暴露未感染儿童群体进行进一步研究。特别是，关于艾滋病毒感染对儿童人群大脑发育的长期影响知之甚少，我们将在拟议的研究中进行调查。 我们有机会获得一个正在进行的纵向神经影像学研究结合几个互补的，非侵入性磁共振成像（MRI）数据集与临床和神经心理学的措施。现有的研究（由R21 MH 096559和R 01 HD 071664资助）一直在跟踪一组儿童，这些儿童自出生以来一直受到密切监测，作为“艾滋病毒儿童早期抗逆转录病毒治疗”（CHER）试验的一部分（艾滋病综合国际研究计划（CIPRA-SA）的一部分，由国家过敏和传染病研究所艾滋病部门赞助）。在第7周，艾滋病毒感染的儿童被随机分配到两个早期ART组之一或延迟ART组。在队列中，艾滋病毒未感染的对照组包括艾滋病毒未暴露，未感染（HUU）和高浓缩铀儿童。在5岁和7岁时，儿童接受临床、神经心理学和神经影像学（结构、弥散和光谱;仅在7岁时进行静息状态功能MRI（RS-FMRI））评估。9年时（从2014年6月开始），将重复相同的多模式成像和评价。 该项目旨在扩大目前的神经影像学措施（根据现有的R 01），包括MR光谱乳酸和脂质浓度，并开发新的多模式标记物，涉及脑网络连接的措施。我们假设这些额外的多模式生物标志物对HIV感染、ART的时机和长期使用以及宫内ART/HIV暴露对大脑发育的影响敏感。该项目扩展了Meintjes博士（开普敦大学）、Laughton博士（斯泰伦博斯大学）和货车der Kouwe博士（马萨诸塞州综合医院）之间的现有合作，包括来自新泽西理工学院（NJIT）的Bharat Biswal博士，他是RS-FMRI分析的主要权威，以及两名UCT早期研究人员Holmes博士和Taylor博士。

项目成果

Repeatability and reproducibility of prospective motion- and shim corrected 2D glycoCEST MRI.

前瞻性运动和垫片校正 2D 糖CEST MRI 的重复性和再现性。

• DOI: 10.21037/qims.2019.09.15
• 发表时间: 2019
• 期刊: Quantitative imaging in medicine and surgery
• 影响因子: 2.8
• 作者: Simegn,GizeaddisLamesgin;Alhamud,Ali;vanderKouwe,AndreJW;Meintjes,Ernesta;Robertson,Frances
• 通讯作者: Robertson,Frances

Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5-11 years in children with perinatal HIV infection.

• DOI: 10.1016/j.neuroimage.2021.118101
• 发表时间: 2021-08-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: van Biljon N;Robertson F;Holmes M;Cotton MF;Laughton B;van der Kouwe A;Meintjes E;Little F
• 通讯作者: Little F

Larger Subcortical Gray Matter Structures and Smaller Corpora Callosa at Age 5 Years in HIV Infected Children on Early ART.

• DOI: 10.3389/fnana.2017.00095
• 发表时间: 2017
• 期刊: Frontiers in neuroanatomy
• 影响因子: 2.9
• 作者: Randall SR;Warton CMR;Holmes MJ;Cotton MF;Laughton B;van der Kouwe AJW;Meintjes EM
• 通讯作者: Meintjes EM

Perinatal HIV Infection or Exposure Is Associated With Low N-Acetylaspartate and Glutamate in Basal Ganglia at Age 9 but Not 7 Years.

围产期 HIV 感染或暴露与 9 岁时基底神经节 N-乙酰天冬氨酸和谷氨酸水平较低有关，但与 7 岁时无关。

• DOI: 10.3389/fnhum.2018.00145
• 发表时间: 2018
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Robertson,FrancesC;Holmes,MarthaJ;Cotton,MarkF;Dobbels,Els;Little,Francesca;Laughton,Barbara;vanderKouwe,AndréJW;Meintjes,ErnestaM
• 通讯作者: Meintjes,ErnestaM