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    Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

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    Author
    Nir, Talia M
    Fouche, Jean-Paul
    Ananworanich, Jintanat
    Ances, Beau M
    Boban, Jasmina
    Brew, Bruce J
    Chaganti, Joga R
    Chang, Linda
    Ching, Christopher R K
    Cysique, Lucette A
    Ernst, Thomas
    Faskowitz, Joshua
    Gupta, Vikash
    Harezlak, Jaroslaw
    Heaps-Woodruff, Jodi M
    Hinkin, Charles H
    Hoare, Jacqueline
    Joska, John A
    Kallianpur, Kalpana J
    Kuhn, Taylor
    Lam, Hei Y
    Law, Meng
    Lebrun-Frénay, Christine
    Levine, Andrew J
    Mondot, Lydiane
    Nakamoto, Beau K
    Navia, Bradford A
    Pennec, Xavier
    Porges, Eric C
    Salminen, Lauren E
    Shikuma, Cecilia M
    Surento, Wesley
    Thames, April D
    Valcour, Victor
    Vassallo, Matteo
    Woods, Adam J
    Thompson, Paul M
    Cohen, Ronald A
    Paul, Robert
    Stein, Dan J
    Jahanshad, Neda
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    Date
    2021-01-04
    Journal
    JAMA Network Open
    Publisher
    American Medical Association
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1001/jamanetworkopen.2020.31190
    Abstract
    Importance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants: This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures: Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results: After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P < .001) and thalamic (mean [SE] β = 32.24 [8.96] mm3 per 100 cells/mm3; P < .001) volumes and larger ventricles (mean [SE] β = -391.50 [122.58] mm3 per 100 cells/mm3; P = .001); in participants not taking cART, however, lower current CD4+ cell counts were associated with smaller putamen volumes (mean [SE] β = 57.34 [18.78] mm3 per 100 cells/mm3; P = .003). A dVL was associated with smaller hippocampal volumes (d = -0.17; P = .005); in participants taking cART, dVL was also associated with smaller amygdala volumes (d = -0.23; P = .004). Conclusions and Relevance: In a large-scale international population of HIV-positive individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Our findings extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era.
    Keyword
    cross-sectional study
    neuroimages
    subcortical brain volume
    Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA). HIV Working Group
    Cognitive Dysfunction
    HIV-1
    Immunosuppression
    Viral Load
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14504
    ae974a485f413a2113503eed53cd6c53
    10.1001/jamanetworkopen.2020.31190
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    UMB Open Access Articles 2021

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