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 M. Nir, J. P. Fouche, Jintanat Ananworanich, Beau M. Ances, Jasmina Boban, Bruce Brew, Linda Chang, Joga Chaganti, Christopher R.K. Ching, Lucette A J Cysique, Thomas Ernst, Joshua Faskowitz, Vikash Gupta, Jaroslaw Harezlak, Jodi Mm Heaps-Woodruff, Charles H. Hinkin, Jacqueline Hoare, John A. Joska, Kalpana J. Kalianpur, Taylor KuhnHei Y. Lam, Meng Law, Christine Lebrun-Frenay, Andrew J. Levine, Lydiane Mondot, Beau K. Nakamoto, Bradford A. Navia, Xavier Pennec, Eric Porges, Cecilia Shikuma, April Thames, Victor G. Valcour, Matteo Vassallo, Adam J. Woods, Paul Murray Thompson, Ronald A. Cohen, Robert H. Paul, Dan J Stein, Neda Jahanshad, for the ENIGMA-HIV Working Group

Research output: Other contributionResearch


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: Lower current CD4+ 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.
Original languageEnglish
Typepre print
Media of outputbioRxiv
Number of pages17
Publication statusPublished - 5 Aug 2021

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