People with chronic HIV exhibit neuroimaging abnormalities compared to people without HIV (PWOH), including lower regional brain volumes. Whether volumetric differences exist during acute HIV (AH) is unknown. The present study examined brain volume by Fiebig stage in a large sample of people with AH (PWAH) enrolled in RV254/SEARCH 010, compared to demographically similar PWOH enrolled in RV304/SEARCH 013.
Participants included 112 Thai males with AH (age 20-46) and 18 male and age-matched (age 18-40) Thai PWOH with no existing co-infections. PWAH were stratified into early (Fiebig I-II; n=32) vs. late (Fiebig III-V; n=80) AH based on Fiebig staging performed after enrollment. T1-weighted scans were acquired using a 3T Philips Ingenia MRI performed within 5 days of ART initiation (on or before day of ART initiation in 64%). Volumes for the caudate, putamen, pallidum, thalamus, amygdala, hippocampus, and nucleus accumbens were summed between hemispheres, corrected for differences in head size, and compared across groups using ANOVAs with false discovery rate for multiple comparisons.
Early AH individuals had equivalent median CD4 T cell count (326 vs. 319 cells/mm3), but significantly lower median CD8 T cell count (366 vs. 648 cells/mm3) and lower average plasma viral load (5.31 vs. 6.42 log10 copies/mL) than late AH individuals (both ps < .01). Late AH individuals exhibited significantly larger volumes in the caudate (11% larger), putamen (31%), pallidum (19%), amygdala (9%), and nucleus accumbens (15%) compared to PWOH (corrected ps < .05; Figure). Late AH individuals also had significantly larger putamen (19% larger) and nucleus accumbens (8%) volumes compared to early AH individuals (corrected ps < .05).
These findings suggest that brain volume in AH varies as a function of duration of infection, indicated by Fiebig stage. Larger volumes in later Fiebig stages may reflect neuroinflammatory processes during acute infection. Longitudinal research is needed to determine whether differences in brain volume persist or resolve after sustained use of ART. Additional examination of immune markers in combination with brain metabolites using spectroscopy will be critical to characterize relationships between brain structure and immune responses after acute infection.