Alterations in brain metabolism during the first year of HIV infection

Abstract

Migration of both uninfected and infected monocytes into the brain during acute HIV infection likely initiates metabolic changes that can be observed with magnetic resonance spectroscopy (MRS). Herein, we measured changes in brain metabolism during the first year of HIV infection and examined the relationship of these metabolite levels to CD16+ monocyte populations measured in the blood. MRS was performed on nine HIV+ subjects identified during acute HIV infection and nine seronegative control subjects. HIV+ subjects were examined within 90 days of an indeterminate Western blot, then again 2 and 6 months later, during early infection. Blood samples were collected for plasma viral RNA and monocyte subset quantification. HIV+ subjects were identified with acute viral ailment and did not display severe cognitive deficits such as dementia or minor cognitive motor disorder. Changes in lipid membrane metabolism (choline levels) in the frontal cortex and white matter were observed during the initial year of HIV infection. Greater numbers of CD16+ monocytes were associated with lower N-acetylaspartate levels and higher choline levels in the brain. These results suggest that HIV infection induces metabolic changes in the brain early during infection and that these changes may be related to monocyte dynamics in the periphery.

Fig. 1

a Representative T2-weighted images of a HIV+ subject indicate the voxel positions in the frontal cortex, white matter (top left), and basal ganglia (top right) examined in both HIV+ and control subjects. b Representative single voxel proton MR spectra from the frontal cortex region of a HIV+ subject at study entry (left spectrum) and 6 months later (right spectrum) during early HIV infection. Six months spectrum was normalized to baseline creatine levels (3.044 ppm). Significant elevations in choline can be seen in this subject after 6 months

Fig. 2

a Changes in brain metabolism which occur during the first year of infection are shown. Examined brain regions included gray matter in the frontal cortex (FC), white matter (WM), and basal ganglia (BG). All measures taken at later time points have been normalized using each HIV+ subject's baseline values. This analysis provides clarity with respect to percent changes in metabolite levels over time. Error bars represent SEM. b Additionally, all MRS values for subjects with early HIV infection have been normalized to control values (dashed line) so that meaningful comparisons between disease and control settings could be made. Error bars represent SEM