Background Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared to that of healthy aging. Methods We examined longitudinal structural brain MRI atrophy rates employing region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants over age 60 years (n=38) compared to age-matched HIV-uninfected healthy and cognitively normal controls (n=24). Results The mean age of participants was 63 years, the mean estimated duration of infection was 21 years and the median of duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, p=0.016), caudate (0.74% vs. 0.03%, p=0.012), frontal lobe (0.48% vs. 0.01%, p=0.034), total cortical gray matter (0.65% vs. 0.16%, p=0.027), brain stem (0.31% vs. 0.01%, p=0.026), and pallidum (0.73% vs. 0.39%, p=0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. Conclusion Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared to healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.

BackgroundHIV RNA is identified in cerebrospinal fluid (CSF) within eight days of estimated viral exposure. Neurological findings and impaired neuropsychological testing performance are documented in a subset of individuals with acute HIV infection (AHI). The purpose of this study was to determine whether microstructural white matter and resting-state functional connectivity (rsFC) are disrupted in AHI.MethodsWe examined 49 AHI (100% male; mean age = 30 ± SD 9.9) and 23 HIV-uninfected Thai participants (78% male; age = 30 ± 5.5) with diffusion tensor imaging (DTI) and rsFC acquired at 3 Tesla, and four neuropsychological tests (summarized as NPZ-4). MRI for the AHI group was performed prior to combination antiretroviral treatment (ART) in 26 participants and on average two days (range:1–5) after ART in 23 participants. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI. Seed-based voxelwise rsFC analyses were completed for the default mode (DMN), fronto-parietal, and salience and 6 subcortical networks. rsFC and DTI analyses were corrected for family-wise error, with voxelwise comparisons completed using t-tests. Group-specific voxelwise regressions were conducted to examine relationships between imaging indices, HIV disease variables, and treatment status.ResultsThe AHI group had a mean (SD) CD4 count of 421(234) cells/mm3 plasma HIV RNA of 6.07(1.1) log10 copies/mL and estimated duration of infection of 20(5.5) days. Differences between AHI and CO groups did not meet statistical significance for DTI metrics. Within the AHI group, voxelwise analyses revealed associations between brief exposure to ART and higher FA and lower RD and MD bilaterally in the corpus callosum, corona radiata, and superior longitudinal fasciculus (p < 0.05). Diffusion indices were unrelated to clinical variables or NPZ-4. The AHI group had reduced rsFC between left parahippocampal cortex (PHC) of the DMN and left middle frontal gyrus compared to CO (p < 0.002). Within AHI, ART status was unrelated to rsFC. However, higher CD4 cell count associated with increased rsFC for the right lateral parietal and PHC seeds in the DMN. Direct associations were noted between NPZ-4 correspond to higher rsFC of the bilateral caudate seed (p < 0.002).ConclusionsStudy findings reveal minimal disruption to structural and functional brain integrity in the earliest stages of HIV. Longitudinal studies are needed to determine if treatment with ART initiated in AHI is sufficient to prevent the evolution of brain dysfunction identified in chronically infected individuals.

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