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Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Talia Nir 1 Jean-Paul Fouche 2 Jintanat Ananworanich 3 Beau Ances 4 Jasmina Boban 5 Bruce Brew 6 Linda Chang 7 Joga Chaganti 6 Christopher R.K. Ching 1 Lucette Cysique 8 Thomas Ernst 7 Joshua Faskowitz 1 Vikash Gupta 1 Jaroslaw Harezlak 9 Jodi Heaps-Woodruff 10 Charles Hinkin 11 Jacqueline Hoare 2 John Joska 2 Kalpana Kallianpur 12 Taylor Kuhn 11 Hei Lam 1 Meng Law 13 Christine Lebrun-Frenay 14 Andrew Levine 15 Lydiane Mondot 16 Beau Nakamoto 12 Bradford Navia 17 Xavier Pennec 18, 19 Eric Porges 20 Cecilia Shikuma 12 April Thames 21 Victor Valcour 22 Matteo Vassallo 23 Adam Woods 20 Paul Thompson 1 Ronald Cohen 20 Robert Paul 24 Dan Stein 2 Neda Jahanshad 1
Abstract : Background: Human immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in chronic and treated HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was established to harmonize data from diverse studies to identify the common effects of HIV-infection on brain structure. Methods: Data were pooled from 12 independent neuroHIV studies from Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1-weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72.4% on cART; 70.3% male; 41.6% with detectable viral load (dVL)), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell count) or dVL. Follow-up analyses stratified data by cART status and sex. Bonferroni correction was used to determine statistical significance. Findings: LowercurrentCD4+ count was associated with smaller hippocampal (β= 20.3 mm3 per 100 cells/mm3; p = 0.0001) and thalamic volumes (β= 29.3; p = 0.003); in the subset of participants not on cART, it was associated with smaller putamen volumes (β= 65.1; p = 0.0009). On average, a dVL was associated with smaller hippocampal (Cohen’s d = 0.24; p = 0.0003) and amygdala volumes (d = 0.18; p = 0.0058). Interpretation: In HIV+ individuals across five continents, smaller limbic volumes were consistently associated with current plasma markers. As we assessed cohorts with different inclusion/exclusion criteria and demographic distributions, these deficits may represent a generalizable brain-signature of HIV infection in the cART era. Our findings support the importance of achieving viral suppression and immune restoration for maintaining brain health. Funding: This work was supported, in part, by NIH grant U54 EB020403.
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Submitted on : Tuesday, January 19, 2021 - 7:14:14 PM
Last modification on : Tuesday, December 7, 2021 - 4:10:58 PM
Long-term archiving on: : Tuesday, April 20, 2021 - 7:59:01 PM


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Talia Nir, Jean-Paul Fouche, Jintanat Ananworanich, Beau Ances, Jasmina Boban, et al.. Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group. 2021. ⟨hal-03063822⟩



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