CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

executive function (p=.026). Figure 1 shows the independent joint component that significantly correlated with global neurocognitive functioning in all three modalities. Gray matter regions included thalamus and cerebellum. White matter regions included the cingulum tract of the cingulate and hippocampus, inferior and superior longitudinal fasciculus, and uncinate fasciculus. Functional regions included posterior parietal, lateral prefrontal, orbitofrontal, anterior cingulate, precuneus, and insular cortices. HIV+ status was associated with lower gray matter volume (p=.038) and lower fractional anisotropy (p=.028) in this component. Duration of HIV disease and nadir CD4 cell count were also associated with gray matter volume and functional connectivity in identified independent components. Conclusion: These results suggest that linked structural and functional deficits in several brain networks are related to HIV-associated NCI. As MRI becomes more commonplace in HIV care, multimodal fusion may provide neural biomarkers to support diagnosis and treatment of NCI.

patterns of volume loss (and potential implications on pathophysiology), and to determine whether age-specific mitigation strategies are warranted in youth. 399 ALCOHOL USE IS ASSOCIATED WITH DEGRADATION OF BRAIN WHITE MATTER IN HIV INFECTION Mollie Monnig 1 , Peter M. Monti 1 , Karen T. Tashima 2 , Joseph Gullett 3 , Eric Porges 3 , Neda Jahanshad 4 , Talia M. Nir 4 , Paul M. Thompson 4 , Ronald Cohen 3 1 Brown University, Providence, RI, USA, 2 The Miriam Hospital, Providence, RI, USA, 3 University of Florida, Gainesville, FL, USA, 4 University of Southern California, Los Angeles, CA, USA Background: Heavy drinking and HIV infection are independently associated with damage to the brain’s white matter. As most neuroimaging studies of people living with HIV (PLWH) exclude heavy drinkers, effects of alcohol use on white matter in the context of HIV are not well understood. We examined associations of current alcohol use, HIV status, and clinical characteristics with indices of white matter integrity in PLWH and seronegative controls. Methods: PLWH and controls were recruited from an immunology clinic for a study of alcohol- and HIV-associated brain dysfunction. Participants were categorized as non-drinkers, moderate drinkers, or heavy drinkers per NIH guidelines. Diffusion tensor imaging was used to derive measures of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Whole-brain voxelwise analyses were performed using tract-based spatial statistics (TBSS), corrected for multiple comparisons. Confirmatory region-of-interest (ROI) analyses were conducted to probe group differences. Results: The sample of 108 participants (62 PLWH, 46 controls) averaged 45.2±11.1 years of age and was 42% female. Most PLWH were on antiretroviral therapy (94%) and were virally suppressed (69%). PLWH and controls were matched on rates of heavy drinking, smoking, and other drug use. In voxelwise analyses, heavier alcohol intake was significantly associated with lower FA, higher RD, and lower AD in widespread areas (p’s<.05; Figure 1). ROI analyses confirmed that non-drinkers had higher FA than heavy drinkers in corpus callosum, cingulate gyrus, posterior thalamic radiation, and left external capsule (p's<.05). Non-drinkers had higher FA than moderate drinkers in genu and body of corpus callosum (p's<.05). Moderate drinkers had higher FA than heavy drinkers in body of corpus callosum, posterior thalamic radiation, and left external capsule (p's<.05). Older age extensively predicted lower FA (p<.05). Neither HIV status nor clinical characteristics were associated with FA, and the HIV by drinking group interaction was not significant (p's>.05). Conclusion: Alcohol use significantly predicted white matter microstructural degradation in this sample of PLWH in care and seronegative controls. Results are consistent with a dose-dependent association of alcohol use with lower white matter microstructural coherence. The overlap between FA and RD maps points to dysmyelination as a possible mechanism. Findings underscore the need to address unhealthy alcohol use in HIV-positive and seronegative individuals.

Poster Abstracts

398 IMPAIRED COGNITION AND REDUCED BRAIN VOLUMES IN YOUTH WITH BEHAVIORALLY ACQUIRED HIV Jennifer McGuire 1 , Robert Brown 2 , Ritobrato Datta 1 , Giulia Fadda 3 , Nichole Tuite 1 , Jacqueline Harrison 1 , Steven D. Douglas 1 , Brenda Banwell 1 1 Children's Hospital of Philadelphia, Philadelphia, PA, USA, 2 McGill University, Montreal, QC, Canada, 3 University of Pennsylvania, Philadelphia, PA, USA Background: Behaviorally acquired HIV infection during adolescence and young adulthood occurs during key brain developmental processes (frontal lobe pruning, network selection). Our prior work suggests deep gray volumes are significantly lower in HIV+ youth vs historical controls; the magnitude of these differences are larger than those reported in adult HIV cohorts despite shorter infection durations and higher CD4+ T-cell nadirs. Here, we aim to compare cognition and deep gray volumes in 16-20-year-old youth with behaviorally acquired HIV versus age-, sex-, and demographically-matched uninfected controls. Methods: Cross sectional analysis of seventeen 16-20-year-old Philadelphia youth with behaviorally acquired HIV (infected for ≥ 1 year) and 18 age-, sex-, and demographically-matched uninfected controls. Participants underwent brain MRI. Brain volumes were measured using FreeSurfer. To evaluate within- structure volumes, voxel-based volume differences between study participants and a standard age-matched atlas were calculated using deformation based T1 morphometry. Results: HIV+ youth and uninfected controls were similar in age (median 20.0 vs 19.5 years), sex (94% vs 94%male), race (88% vs 94% African American), insurance status, and average alcohol and marijuana consumption. The median infection duration for HIV+ youth was 1.9 years (IQR 1.4-2.9), and median CD4 nadir was 410 cells/uL (IQR 335-478). 69% (11/16) of HIV+ youth qualified for a diagnosis of HIV-associated neurocognitive disorder, 9 with functional impairment. Total intracranial volume did not differ between HIV+ youth and controls, but HIV+ youth had 7% lower caudate volumes compared to controls (p=0.052); volume differences within the caudate were more pronounced in regions proximal to the CSF interface. Cognitive impairment was associated with lower thalamic volumes in HIV (p=0.002), but not in controls. Conclusion: These data support the concept that youth with behaviorally acquired HIV have early volume loss in deep gray structures despite robust CD4+ T-cell counts, and that volume loss is associated with cognitive impairment. Larger longitudinal studies with adult comparators are needed to further define

400 MICROSTRUCTURAL MRI CHANGES ASSOCIATED WITH COGNITIVE IMPAIRMENT IN CONTROLLED HIV Elizabeth F. Horne 1 , Gina Norato 1 , Lillian Ham 2 , Joseph Snow 2 , Daniel S. Reich 1 , Bryan Smith 1 , Govind Nair 1 , Avindra Nath 1 1 National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA, 2 NIH, Bethesda, MD, USA

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