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

Talia Nir 1 Jean-Paul Fouche 2 Jintanat Ananworanich 3, 4 Beau Ances 5 Jasmina Boban 6 Bruce Brew 7 Joga Chaganti 7 Linda Chang 8, 9 Christopher Ching 1 Lucette Cysique 10 Thomas Ernst 8, 9 Joshua Faskowitz 1 Vikash Gupta 1 Jaroslaw Harezlak 11 Jodi Heaps-Woodruff 12 Charles Hinkin 13 Jacqueline Hoare 2 John Joska 2 Kalpana Kallianpur 9 Taylor Kuhn 13 Hei Lam 1 Meng Law 14 Christine Lebrun-Frénay 15, 16 Andrew Levine 13 Lydiane Mondot 15, 16 Beau Nakamoto 9 Bradford Navia 17 Xavier Pennec 16, 18 Eric Porges 19 Lauren Salminen 1 Cecilia Shikuma 9 Wesley Surento 1 April Thames 20 Victor Valcour 21 Matteo Vassallo 22 Adam Woods 19 Paul Thompson 1 Ronald Cohen 19 Robert Paul 23 Dan Stein 2 Neda Jahanshad 1
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 drawnto date.OBJECTIVE To examine structural brain associations with the most commonly collected clinicalassessments of HIV burden (CD4+T-cell count and viral load), which are generalizable acrossdemographically and clinically diverse HIV-infected individuals worldwide.DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study established the HIV WorkingGroup within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortiumto pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and NorthAmerica. Regional and whole brain segmentations were extracted from data sets as contributingstudies 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 wereextracted from T1-weighted magnetic resonance images to identify associations with blood plasmamarkers of current immunosuppression (CD4+T-cell counts) or detectable plasma viral load (dVL) inHIV-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 wereassociated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3per 100 cells/mm3;P< .001)and thalamic (mean [SE] β = 32.24 [8.96] mm3per 100 cells/mm3;P< .001) volumes and largerventricles (mean [SE] β = −391.50 [122.58] mm3per 100 cells/mm3;P= .001); in participants nottaking cART, however, lowercurrent CD4+cell counts were associated with smaller putamen volumes(mean [SE] β = 57.34 [18.78] mm3per 100 cells/mm3;P= .003). A dVL was associated with smallerhippocampal volumes (d= −0.17;P= .005); in participants taking cART, dVL was also associated withsmaller amygdala volumes (d= −0.23;P= .004)
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Submitted on : Saturday, May 29, 2021 - 3:23:06 PM
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Talia Nir, Jean-Paul Fouche, Jintanat Ananworanich, Beau Ances, Jasmina Boban, et al.. Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV. JAMA Network Open, American Medical Association, 2021, 4 (1), pp.e2031190. ⟨10.1001/jamanetworkopen.2020.31190⟩. ⟨hal-03241929⟩



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