167 – Brain Volume Normalization After 96 Weeks of ART Started During Acute HIV Infection

Background

Previous studies on brain volumes in people with HIV (PWH) who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) were limited by the absence of a control group or brief follow-up periods. A recent cross-sectional analysis revealed larger volumes in regions vulnerable to HIV during AHI. Here, we compared longitudinal brain volume changes over 96 weeks between RV254 AHI cohort participants and people without HIV (PWoH).  

Methods

The study included 119 RV254 AHI cohort participants and 45 demographically matched PWoH from Thailand, all of whom underwent two 3T brain MRI approximately 96 weeks apart. RV254 participants underwent the 1^st MRI and completed the Patient Health Questionnaire (PHQ-9) for depressive symptoms, and a 4-test cognitive battery during AHI and prior to ART initiation at week 0. AHI participants achieved HIV suppression by week 24, and underwent the 2^nd MRI at approximately 96 weeks post-ART. Brain volumes were quantified using voxel-based morphometry and summed across hemispheres. Repeated measures compared volumes within and between the groups. Correlations examined associations between brain volumes with cognitive performance (NPZ-4) and the PHQ-9 score at week 0 for the PWH group, with adjustments for multiple comparisons.  

Results

Both groups were similar in age, education, and comorbidities. All RV254 participants were male, with a median age of 28, median CD4+ T-cell count of 412 (IQR 277-664) cells/mm³, and median plasma HIV RNA of 6.66 (IQR 5.73-6.90) log₁₀ cps/ml at week 0. Both groups exhibited smaller brain volumes in most regions at week 96 compared to week 0 with no evidence of accelerated volume loss among PWH. At week 0, larger volumes were observed among PWH compared to PWoH in the hippocampus and thalamus with no differences between groups at week 96, consistent with normalization after ART. Amygdala and nucleus accumbens volumes were lower among PWH at week 0 without progressive volume loss. Among the AHI participants, larger hippocampal and caudate volumes at week 0 correlated with worse depressive symptoms and lower NPZ-4 score  (p<.05). 

Conclusions

We observed no evidence of more rapid brain atrophy in these young, healthy AHI individuals who initiated ART during acute infection compared to healthy PWoH. Larger brain volumes in select regions at week 0 (pre-ART) correlated with worse neurobehavioral indices, with normalization in brain volumes following sustained viral control.