January 25, 2021
Combination antiretroviral therapy (cART) has shifted HIV infection from a fatal to a chronic condition. New evidence now suggests this has been accompanied by a shift in the profile of HIV-related brain abnormalities beyond the basal ganglia, frequently implicated in the pre-cART era, to limbic structures.
"This shift in subcortical signatures may be contributing to the increasing range of neuropsychiatric and cognitive outcomes," write Neda Jahanshad, PhD, University of Southern California Keck School of Medicine, and colleagues.
The study was published online January 15 in JAMA Network Open.
Brain Signature of HIV
The researchers with the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium examined structural brain associations with CD4+ T cell counts and HIV viral load.
These clinical markers are the most consistently available in studies of HIV and generalize across demographically and clinically diverse HIV-infected individuals, they point out. However, the degree to which they capture central nervous system (CNS) injury is not fully understood.
In this cross-sectional study of 1203 HIV-infected adults from 13 HIV neuroimaging studies, a lower CD4+ T-cell count was associated with smaller hippocampal and thalamic volume independent of treatment status. However, in a subset of adults not on cART, a lower CD4+ T-cell count was associated with smaller putamen volume.
Across all participants, detectable viral load was associated with smaller hippocampal volume, but in the subset on cART, detectable viral load was also associated with smaller amygdala volume.
The findings indicate that plasma markers universally used to monitor immune function and response to treatment in patients with HIV infection are associated with subcortical brain volume.
"Our findings," they add, "extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era."
A limitation of the analysis is that most of the participants were men (n = 880, 73%). "A more extensive international effort assessing the neurologic effects of HIV infection in women is needed," they conclude.
This analysis, they add, demonstrates the feasibility and utility of a global collaborative initiative to understand the neurologic signatures of HIV infection. They invite other HIV researchers to join the ENIGMA-HIV consortium.
"With a greater collaborative effort, we will be able to assess factors that may modulate neurologic outcomes, including cART treatment regimens, comorbidities, coinfections, substance use, socioeconomic factors, and demographic factors, as well as the functional implications of such structural brain differences, in well-powered analyses," the researchers say.
"Understanding the neurobiological changes that may contribute to neuropsychiatric and cognitive outcomes in HIV-positive individuals is critical for identifying individuals at risk for neurologic symptoms, driving novel treatments that may protect the CNS, and monitoring treatment response," they add.
Support for this research was provided by grants from the National Institutes of Health, the SA Medical Research Council, the National Health and Medical Research Council and the European Research Council. Jahanshad received partial research support from Biogen Inc for work unrelated to the topic of this article. A complete list of author disclosures is in the original article.