CROI 2016 Abstract eBook

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Poster Abstracts

(Magnus et al., CROI 2014), suggesting ACC dysfunction might underlie executive dysfunction in HIV. Here, we further investigated the brain dysfunction in the cingulate cortex using resting-state functional connectivity MRI (rs-fcMRI). Methods: Thirty-eight adults (43-63 years old, 23 HIV+ on antiretroviral therapy) without major psychiatric disorders and other confounding health problems participated in this study. HIV+ and HIV- subjects did not differ significantly on a battery of standard neuropsychological tests. One run of rs-fcMRI data was collected. After controlling for confounding parameters, we extracted the time series from the posterior, middle, and anterior regions of cingulate, then obtained the two sets of voxel-wise correlations, R wi , within each region, and R btw , between two different regions. The disruption to cingulate connectivity (Icc) was defined as I cc = (R wi - R btw ) / (R wi + R btw ) with higher I cc represents more reduced inter-regional connection. Results: Results are shown in Figure 1. (A) Two-sample t-test revealed an increase in I cc due to HIV. (B) Pearson’s correlation analysis revealed a significant correlation between age and I cc . (C) For a subset of subjects from the Magnus et al. (2014) study, there was a significant correlation between I cc and the cost of task switch (the difference between the task-switch and non-switch trial) in fMRI at ACC, suggesting the disconnection between cingulate regions might contribute to the disrupted neural activity in ACC and executive dysfunction in HIV. Conclusions: The rs-fcMRI technique revealed that both aging and HIV disrupt the connection between different cingulate regions. The disrupted connections correlate with the disrupted brain activations in the ACC. These results suggest that the cingulate might be one of brain regions affected early on during the evolution of HIV brain disease, and the additive impairments due to aging and HIV might underlie the increased risk of executive deficits in HIV+ older adults.

391 Multifactorial Neurochemical Alterations Are Slowly Evolving Despite Viral Control Lucette A. Cysique 1 ; Laurianne Juge 2 ;Thomas M. Gates 3 ; Kirsten Moffat 3 ; Bruce J. Brew 1 ; Caroline Rae 1 1 Univ of New South Wales, Sydney, Australia; 2 NeuroSci Rsr Australia (NeuRA), Randwick, Australia; 3 St Vincent’s Hosp, Darlinghurst, Australia Background: Chronic HIV infection in the context of long-term viral suppression and aging represents a new context for HIV neuropathogenesis research. While HIV-related brain injury can be detected using in vivo proton Magnetic Resonance Spectroscopy ( 1 H-MRS) in HIV+ persons, the evolution of such brain damage is unclear. Methods: The study sample included 108 men (mean age=55±6), 73 were HIV+ (71%with historical AIDS, nadir CD4 ≤350, all on antiretroviral treatment; baseline plasma and CSF viral suppression>97%; follow-up plasma suppression>94%); and 35 demographically comparable HIV-uninfected controls. All underwent 1 H-MRS of the frontal white matter (FWM), the posterior cingulate cortex (PCC) and the caudate area (CA) at baseline and 18-months later. Neurocognitive performance was also examined at the same time points. Major brain metabolites: Creatine ( Cr ), N -Acetyl Aspartate ( NAA ), Choline ( Cho ), Glutamate ( Glu ) and Myo -Inositol ( MI ) were fitted in jMRUI in reference to H 2 O. Change in brain metabolites was determined using linear regression with a time effect, a group effect and a time*group interaction effect. Age, HIV disease and treatment and cardiovascular markers, having a history of HAND, baseline neurocognitive performance and neurocognitive change were evaluated as predictors/covariates in voxels where significant HIV status-related neurochemical changes were found. Results: Across the study period, in the HIV+ sample and relative to HIV- controls, FWM Cr ( p <.01), PCC Cr (p<.01) CA Cr (p<.05), PCC NAA (p<.01) and CA NAA (p<.05) were reduced; PCC MI (p<.05) was elevated. Chronological age did not predict these between-group differences. When only considering the HIV+ sample, lower baseline neurocognitive performance was associated with lower CA NAA (p<.05) over time. History of HAND was associated with reduced FWM Cr (p=.01), lower PCC NAA (p<.05), and lower PCC Cr over the study period (p<.05). Viral blips (n=6) were associated with reduced PCC NAA over time (p<.05). History of cardiovascular disease was associated with lower PCC NAA and Cr over time (p<.05). Conclusions: Metabolite abnormalities were stable over time and included widespread decreased cellular energy (related to glial activation in a neuroAIDS macaque model), cortical and subcortical neuronal integrity loss and restricted neuroinflammation. Predictor/Covariate findings support slowly evolving multi-dimensional neuropathogenesis emphasizing the need for long-termmonitoring of brain functions in chronic HIV infection.

Poster Abstracts

148

CROI 2016