Longitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection

Abstract

Background: Human immunodeficiency virus (HIV) penetrates the brain in early infection. We used neuroimaging to longitudinally examine the impact of HIV and combination antiretroviral therapy (cART) on the brain in treated and untreated HIV-infected participants, starting in primary HIV infection (PHI).

Methods: Sixty-five participants, enrolled during PHI, underwent longitudinal magnetic resonance imaging, 30 of whom commenced cART during follow-up. Cross-sectional data from 16 patients with chronic HIV infection (CHI) and 19 HIV-uninfected participants were included for comparison. Brain volume and cortical thickness were estimated using tensor-based morphometry and cortical modeling, respectively. Mixed-effects models longitudinally mapped structural brain changes before and after cART. The relationship between brain morphometry estimates and blood and cerebrospinal fluid (CSF) biomarkers were also tested. Region-of-interest analyses were performed to compare brain morphometry estimates between the groups.

Results: Prior to cART, longer duration of untreated infection in PHI correlated with volume loss in the thalamus, caudate, and cerebellum, and with cortical thinning in the frontal and temporal lobes and cingulate cortex. After cART, no further volume loss was observed. However, small increases of cortical thickness in the frontal and temporal lobe correlated with longer cART duration. No correlations were observed with blood or CSF measures. The PHI group did not have different brain morphometric measures compared to the HIV-uninfected group, but had larger volumes in the thalamus, caudate, putamen, and cortical gray matter compared with CHI participants.

Conclusions: Subcortical atrophy and cortical thinning occur during untreated infection but may be arrested by cART. These findings emphasize the importance of early cART.

Figure 1.

A, Upper row: Brain volume loss associated with longer duration of untreated infection as revealed with tensor-based morphometry. Lower row: Volume of the right cerebellum (left plot) and bilateral thalami (right plot) in relation to the duration of infection. B, Upper row: Cortical thinning associated with longer duration of untreated infection (left) and longer combination antiretroviral therapy (cART) duration (right). Lower row: Cortical thickness of the right superior temporal gyrus (left) and right frontal lobe (right) in relation to the duration of infection for all participants with primary human immunodeficiency virus infection. All brain maps were thresholded at false discovery rate of 5%.