Longitudinal changes in brain structure and integrity during acute HIV

Cognitive impairment persists in the form of HIV-associated neurocognitive disorder (HAND) among chronically infected individuals despite successful viral suppression. Widespread access to combination antiretroviral therapy (cART) has allowed infected individuals to initiate treatment at an earlier time point and effectively reduce the risk of HIV-related mortality and morbidity. The current study examines whether cART, when initiated within days to weeks following infection, can longitudinally preserve brain health. Quantitative magnetic resonance image (MRI) methodologies were used to analyze T1-weighted structural images and diffusion tensor imaging (DTI) metrics. Specifically, region of interest and voxel-wise volume and tensor-based spatial statistics (TBSS) approaches were performed to evaluate differences in brain volumes and white matter microstructure. We examined 31 acute HIV (AHI) participants who had paired month 0 (baseline) and month 24 (two-year follow-up) scans. Participants were comparatively analyzed in both a longitudinal manner to themselves, and a cross-sectional manner against 25 healthy control (CO) participants. As an indication of inflammation, CD8 t-lymphocyte counts was examined as a clinical covariate. The 31 AHI participants had a median (IQR) age of 26 (23-30) years at the time of enrollment and a median (IQR) baseline CD4 count of 576 (370-868) cells/μL. All immediately initiated cART. The 25 healthy controls had a median (IQR) age of 31 (26-37) years. Differences of brain integrity in the AHI group followed longitudinally were observed. Baseline CD8 count was significantly associated with increased mean diffusivity (MD) in the longitudinally infected, present in the genu and the splenium of the corpus callosum, the corona radiata, and the superior longitudinal fasciculus (all p<0.05). Structural analysis revealed enlarged corpus callosum (p<0.01) volumes, as well as enlarged caudate and thalamus subcortical gray matter volumes in the longitudinally infected AHI participants (both p<0.05). Differences of brain integrity in the AHI group after 24 months of treatment were observed compared to healthy controls. Specifically, fractional anisotropy (FA) was reduced in AHI at 24 months compared to controls in models adjusting for age in the corpus callosum, the corona radiata, and the left superior longitudinal fasciculus (all p<0.05). Structural analyses revealed enlarged putamen and the caudate volumes (both p<0.05). We conclude that differences in both brain integrity and structural volumes can be seen in AHI with successful viral suppression when compared to healthy controls. Future work will include longitudinal imaging data from healthy controls who are followed over two-year follow-up to ensure that observed changes are disease specific. We will also comparatively investigate longitudinally treated chronic HIV-infected participants (‘positive controls’) to examine if the differences are similar to those seen when therapy is initiated in the chronic stage of infection. We will examine inflammatory plasma and CSF biomarkers to inform potential mechanisms and, separately, cognitive testing to inform clinical significance