HIV penetrates the brain early in infection. However, brain volume changes that occur during this period and the effect antiretroviral therapy (ART) has on these changes are unclear. To explore this issue, we used tensor-based morphometry (TBM) and cortical modeling to examine the longitudinal trajectory of regional brain volumes and cortical thickness in treated and untreated primary HIV-infected (PHI) participants.
PHI participants (<1 year after exposure) in the PISCES cohort from San Francisco underwent longitudinal MRI. Several participants commenced ART during follow-up. TBM and cortical modeling estimated regional brain volumes and cortical thickness, respectively. A two-phase mixed-effect model assessed the trajectory of our MRI measures before and after ART. This involved fitting a linear model at time points before ART initiation and a different linear model at time points after ART. Both models were constrained to meet at the time of ART initiation. Additional mixed-effect models assessed correlations of regional MRI measures with CD4+ and CD8+ cell counts, CD4/CD8 ratio, and CSF and blood HIV RNA at time points before ART.
65 male PHI participants enrolled ((mean±SD) age 36.8±9 year, education 15.4±2.3 year, duration of infection 4.2±2.5 month, MRI per participant 2.5±1.5). Prior to ART initiation, we observed that longer duration of infection was correlated with brain volume loss in the thalamus, caudate, temporal lobe and cerebellum as shown by TBM (see Fig 1 for voxel-wise statistics), and with cortical thinning in the frontal and temporal lobes, as well as middle cingulate cortex (p<.05) (Fig 1B). After ART initiation, no further significant brain volume changes were found by TBM (Fig 1A). However, small but statistically significant increases of cortical thickness in the right frontal and temporal lobes correlated with longer ART duration (p<.05) (Fig 1B). Before ART, increased CSF HIV RNA was related with volume reductions in the thalamus (p<0.1) (Fig 1C). CD4+ cell count and CD4/CD8 ratio were positively correlated with cortical thickness in the left frontal lobe (p<.05) (Fig 1D).
Regional subcortical volume loss and cortical thinning occur before ART initiation. However, initiating ART can halt further structural deterioration. These findings support the hypothesis that brain injury due to HIV occurs during untreated infection and worsens in the absence of ART. This suggests that early initiation of ART preserves long-term brain health.