CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

for HIV+ individuals was as follows: normal cognition- (n= 11), asymptomatic neurocognitive impairment (ANI)- (n= 12), mild neurocognitive disorder (MND)- (n= 10) , HIV dementia- (n= 10). There were no differences in median global cortical uptake stratified by HAND stage or HIV serostatus. However, the median global cortical SUVR uptake for HIV+ individuals in their 50’s, 60’s, and 70’s were 1.47, 1.31, and 1.26 respectively, whereas for HIV- individuals, they were 1.37, 1.41, and 1.58, respectively (non-significant), suggesting a trend for increased global cortical amyloid uptake at an earlier decade of life among HIV+ individuals. For 50 year olds, HIV+ individuals had increased uptake in the posterior cingulate cortex [median (IQR) = 1.59 (1.44-1.80)] compared to HIV- individuals [median (IQR) = 1.43 (1.25-1.45)], (p =0.038). Conclusion: Amyloid deposition as measured by PET imaging may occur at an earlier age in HIV+ individuals > age 50 compared to age matched HIV- individuals suggestive of premature aging in the brain. However, amyloid deposition did not correlate with cognitive impairment. Further longitudinal studies of PET amyloid imaging and cognition in older HIV+ individuals are warranted. 439 NEUROIMAGING CORRELATES OF FRAILTY, COGNITION, AND HIV Jeremy Strain , Robert S. Smith, Sarah Cooley, Beau M. Ances Washington University St Louis, St Louis, MO, USA Background: Chronically infected HIV+ patients are afflicted with a variety of age-related comorbities that can manifest as cognitive sequelae. Frailty is a phenotypic assessment that examines different physical attributes as a generic metric for secondary anatomical etiologies. In a data driven approach we assessed the relationship between brain integrity (neuroimaging [functional and structural] and neuropsychological performance) and frailty in an HIV+ population. Methods: 89 HIV+ patients, ranging in age from 50 to 85 (M=57.4; SD=6.43), were dichotomized as either frail (≥3)(n=11) or non-frail (<3)(n=78) using the Fried criteria. Global deficit scores (GDS) and domain specific scores (executive, psychomotor speed, and memory) were derived from a NP battery of tests. Voxel-wise comparisons with a cluster-based technique were performed on resting cerebral blood flow (rCBF) comparing non-frail and frail HIV+ participants. The CBF cluster analysis yielded 8 regions of interest (ROIs) that showed significantly lower CBF in frail compared to non-frail HIV+ individuals. These CBF ROI clusters served as seeds for probabilistic white matter tractography. Results: A significant association was seen for average fractional anisotropy (FA) and CBF for the four (bilateral frontal poles, anterior cingulate and posterior cingulate) structurally connected regions (p<0.001). Average FA, for white matter connecting the four regions, was significantly decreased in frail compared to non-frail HIV+ individuals (p=0.017). Lower FA values were also associated with worse cognition (both global (p=0.001) and executive domain (p=0.022)). Both CBF and FA significantly predicted GDS outcome (p=0.009) but only CBF significantly improved the model (p=0.034). Conclusion: We conclude that HIV+ frail individuals have reductions in rCBF and associated reductions in structural connections between these areas. Both lower CBF and reduced FA in these ROIs predicted poorer cognitive performance suggesting a possible etiology to the behavioral changes associated with the frailty index. This multi-modality approach suggests that the frailty index is capable at identifying secondary pathologies that reflects accentuated functional and structural damage in HIV+ individuals. 440 SUBCLINICAL GLOBAL AND THALAMIC HYPOMETABOLISM ON FDG-PET IN TREATED HIV+ SUBJECTS Dima A. Hammoud , Sanhita Sinharay, Sally Steinbach, Paul Wakim, Katrina Geannopoulos, Katherine Traino, Amit Dey, Stanley Rapoport, Edmund C. Tramont, Joseph Snow, Nehal N. Mehta, Bryan Smith, Avindra Nath NIH, Bethesda, MD, USA Background: Despite improved life expectancy in HIV seropositive (HIV+) individuals, HIV-associated neurological disorders (HAND) remain a major morbidity. The specific neuronal populations that contribute to HAND however are unknown. 18F-Fluoro-Deoxyglucose Positron Emission Tomography (FDG- PET) quantitatively measures glucose metabolism in the brain and can identify regional differences in neuronal function. Methods: We used brain FDG-PET imaging to evaluate optimally-treated, virologically-suppressed HIV+ individuals (n=47), compared to age-matched healthy controls (HCs; n=19) and to a group of HIV seronegative (HIV-; n=11)

age-matched subjects from the same socio-economic background, sharing many of the comorbidities seen in the HIV+ group. We compared global and regional FDG standardized uptake values (SUV) (subcortical/central structures) amongst the groups and correlated them to various clinical variables and to neuropsychological assessments at the time of the scanning. Whole brain SUVmean and SUVmax were measured for all subjects and compared. Regional uptake values (SUVmean, SUVmax and relative SUVmean = regional SUVmean/ Whole brain SUVmean) were also assessed in the caudate, putamen, thalamus, and cerebellum. Results: We found statistically significant lower whole brain SUVmax in HIV+ compared to HC but not to HIV-. Among subregions, only thalamic relative SUVmean values were significantly lower in HIV+ compared to HC and to HIV- subjects (Figure.1). Using a mixed-effect statistical model, the most predictive clinical variables for reduced thalamic relative SUVmean was group (HIV status) and prior drug use. Considering the HIV+ group separately, cardiovascular disease risk (measured as the 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk) correlated with most of the other SUV values. Conclusion: HIV+ and HIV- subjects with similar co-morbidities showed global hypometabolism compared to HC suggesting an important role for those co-morbidities, especially cardiovascular disease, in neuronal loss/dysfunction. Of the four regions measured, only the thalamus showed significantly lower relative SUVmean values in HIV+ compared to HIV-, possibly reflecting a specific effect of the virus, and potentially explaining memory, executive functioning and attention deficits in this patient population.

Poster Abstracts

441LB BRAIN PET IMAGING OF MICROGLIA IN MACAQUES WITH SIV ENCEPHALITIS

Dima A. Hammoud , Sanhita Sinharay, Kenta Matsuda, Dianne Lee, Swati Shah, William Reid, Paul Wakim, Vanessa Hirsch, Avindra Nath, Michele Di Mascio NIH, Bethesda, MD, USA Background: Microglial activation (neuroinflammation) is hypothesized to play a central role in neuronal damage associated with HIV. In this study we wanted to image the translocator protein (TSPO), a mitochondrial membrane receptor overexpressed in activated microglia in macaques infected with a neuro-tropic SIV strain (SIVsm804E), before and after inoculation, using [18F]- DPA714 PET. Methods: Dynamic PET imaging with [18F]-DPA714 followed by displacement with cold PK11195 (TSPO antagonist) was performed in 5 SIV-infected macaques at baseline as well as different time points following inoculation. Regional and whole brain volumes of interest were drawn on the respective MR images and specific/total binding was calculated as standardized uptake values (SUV) at equilibrium using PMOD 3.7. Multiplex post-mortem immunofluorescent (IF) staining for microglia/macrophages (iba1), neurons (NeuN), and apoptosis (cleaved caspase-3/PARP) was performed in all animals and compared to 3 normal monkey brains. Correlation of SUV values with cerebrospinal fluid (CSF) and plasma viral load (VL) was also performed.

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