CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

without FHD ( p = 0.83). Examining inheritance type (maternal vs. paternal), type of dementia (AD vs. non-AD), or number of relatives with a dementia diagnosis did not strengthen these associations. A median split was conducted on raw CSF A β -42 values to create high and low CSF A β -42 groups and showed that those with low CSF A β -42 and FHD had the highest prevalence of HAND (74%), while the remaining groups were similar (high CSF A β -42 FHD: 49%; high CSF A β -42 no FHD: 52%; low CSF A β -42 no FHD: 57%). Post-hoc analyses showed that the CSF A β -42 X FHD interaction trend was driven by speed of information processing ( p = 0.01). Conclusions: FHD moderates the effect of CSF A β -42 on HAND. These findings highlight the complexities of analysis of biomarkers of age-related neurodegeneration in HAND. 484 Cystatin C Is AssociatedWith Neurocognitive Impairment in Older HIV+ Adults Marissa Sakoda 1 ; Pariya L. Fazeli 2 ; Scott Letendre 2 ; Dilip Jeste 2 ; Igor Grant 2 ; David J. Moore 2 1 John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI, US; 2 University of California San Diego, San Diego, CA, US Background: The incidence and prevalence of HIV infection among older adults is on the rise. Older age appears to increase the risk of neurocognitive impairment (NCI) among HIV+ adults. Understanding the correlates of NCI in older HIV+ adults is important, particularly biomarkers in readily accessible body fluids. Among older HIV- adults, elevated cystatin C predicts neurocognitive (NC) decline and mortality. Cystatin C is elevated in HIV+ persons, but the association of cystatin C and NCI has yet to be studied. Our goal was to examine differences in cystatin C between HIV+ and HIV- older adults, and, within the HIV+ adults, to examine the association of cystatin C with NCI. Methods: Participants were 77 HIV+ and 47 HIV- older adults (50 years or older) enrolled in a cross-sectional study at UCSD’s HIV Neurobehavioral Research Program. HIV+ participants were taking suppressive antiretroviral therapy. Cystatin C was measured in blood plasma by immunoassay. A standardized comprehensive neurocognitive assessment was performed. NCI was based on domain and global deficit scores derived from demographically corrected T-scores. Results: The HIV+ group had a significantly higher cystatin C concentration than the HIV- group ( p <0.001). In the HIV+ group, higher cystatin C levels were associated with NCI (d=0.42, p =0.0549) and were not statistically significant in the HIV- group (d=0.12, p =0.70). Recursive partitioning identified that HIV+ subjects who had cystatin C levels ≥ 0.75 mg/L had a 79% increased relative risk of NCI (p=0.02). In a multivariable model that included relevant covariates (e.g., gender, race, depression), higher cystatin C levels remained associated with NCI ( p =0.02). Conclusions: HIV+ adults had higher cystatin C concentrations than HIV- adults, consistent with prior reports. Higher plasma cystatin C was associated with NCI in older HIV+ adults but not in HIV- adults. Cystatin C may be a useful clinical biomarker to identify HIV-infected persons at increased risk for NCI. A significant limitation of the present study is the cross-sectional design. Future projects should investigate the role of cystatin C in neurocognitive decline over time among older persons living with HIV. 485 Leptomeningeal Enhancement on MRI in the Aging HIV-Positive Population Bryan R. Smith 1 ; Sally Steinbach 1 ; Govind Nair 1 ; Caryn Morse 1 ; Joseph Snow 2 ; Suad Kapetanovick 2 ; Henry Masur 1 ; Avindra Nath 1 ; Daniel S. Reich 1 1 National Institutes of Health, Bethesda, MD, US; 2 National Institute of Mental Health, Bethesda, MD, US; 3 National Institutes of Health, Clinical Center, Bethesda, MD, US Background: HIV infection is associated with neurologic sequelae that may be related to chronic CNS inflammation despite treatment with antiretroviral therapy (ART). Objective biomarkers of CNS involvement with HIV infection are needed to identify patients at risk of neurologic complications. Leptomeningeal contrast-enhancing lesions on MRI have been described recently in multiple sclerosis, a neuro-inflammatory disorder, where they correspond pathologically to perivascular lymphocytic and mononuclear infiltration of the leptomeninges. However, such foci have not been described in the HIV-positive population. This study explored the prevalence of leptomeningeal contrast-enhancing lesions in the HIV-positive population and possible clinical correlations. Methods: Brain MRI, using an optimized 3D post-contrast T2-weighted fluid-attenuated inversion recovery (FLAIR) technique, was collected in 51 HIV-positive and 10 HIV- negative participants in a cross-sectional study of HIV and cognition. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Results: Focal contrast enhancement was detected in the leptomeningeal compartment in 13/51 HIV-positive cases (25%) vs. 0/10 HIV-negative cases (0%; p=0.07). Demographics (age, race, sex) and clinically relevant medical variables (systolic blood pressure, c-reactive protein values, diabetes mellitus and chronic hepatitis C status) were similar between HIV-positive and HIV-negative groups. All HIV-positive participants were receiving ART, and 50/51 had a plasma HIV viral load <40 copies/ml at the time of evaluation. Within the HIV-positive group, advanced age was the only clinical factor associated with leptomeningeal enhancement (p = 0.029). HIV-positive participants with leptomeningeal enhancement had a mean age of 55.3 yrs compared to 49.1 yrs in participants without enhancement. There was no correlation with CD4 cell count, CD4 nadir, duration of HIV infection, or history of neurologic disorders. Conclusions: A subset of HIV-positive individuals on ART have contrast-enhancing multifocal lesions in the leptomeningeal compartment on MRI. This finding is more common with advanced age. Longitudinal studies are needed to identify whether this novel imaging technique has prognostic significance in older HIV-positive individuals.

Poster Abstracts

Sagittal MRI 3D post-contrast fluid-attenuated inverse recovery (FLAIR) image of an HIV-positive patient demonstrating a leptomeningeal contrast-enhancing lesion (arrow). Conclusions: A subset of HIV-positive individuals on ART have contrast-enhancing multifocal lesions in the leptomeningeal compartment on MRI. This finding is more common with advanced age. Longitudinal studies are needed to identify whether this novel imaging technique has prognostic significance in older HIV-positive individuals.

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CROI 2015