Elevated neurotransmitter levels in people with HIV are associated with attention function

People with HIV (PWH) often exhibit cognitive impairments, particularly in attention and executive function domains, despite effective viral suppression. The neurophysiological and neurochemical mechanisms underlying these deficits remain poorly understood. Herein, we used proton magnetic resonance spectroscopy ( 1 H-MRS) at 3 T with spectral editing to quantify the inhibitory (GABA+: GABA and co-edited macromolecules) and excitatory (Glx: glutamate and glutamine) neurotransmitter pools in the calcarine cortex of 27 virally suppressed PWH and 27 age- and sex-matched controls. We also estimated several secondary metabolites commonly implicated in neuroinflammatory and energetic processes, including total N -acetylaspartate (tNAA), total choline (tCho), total creatine (tCr), and myo-inositol (mI). Following best practices, metabolite concentrations were scaled to the unsuppressed water signal and corrected for voxel tissue composition, including gray matter, white matter, and CSF percentages. Compared with controls, PWH exhibited significantly elevated GABA+, Glx, and mI levels, suggesting parallel alterations in inhibitory, excitatory, and glial pathways. Notably, higher Glx levels were associated with longer HIV disease duration and increases in Glx and mI were coupled to decreases in attentional performance, linking neurochemical alterations to both disease progression and cognitive dysfunction. In sum, these findings provide the first evidence of concurrent GABA+ and Glx alterations in virally suppressed PWH, supporting a model in which disrupted excitatory-inhibitory balance contributes to cortical instability and attentional deficits in HIV. • People with HIV exhibit cognitive decline more often than the general population. • Altered neurotransmitter levels may contribute, but evidence is currently limited. • MR spectroscopic data was collected on matched people with HIV (PWH) and controls. • PWH exhibited elevated GABA+, Glx, and myo-inositol levels in calcarine cortex. • Glx predicted disease duration in PWH and attention performance in all participants.