CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Background: Despite cART, cognitive impairment and brain MRI abnormalities are still prevalent in people with HIV (PWH). Diffusion tensor imaging (DTI) can be used to detect microstructural changes in both white matter (WM) and grey matter (GM), and it may be possible to detect subtle and early changes prior to neurocognitive decline. In this cross-sectional study, we investigated integrity of the brain parenchyma in virologically controlled PWH (HIV+) and socio- economically similar control subjects (HIV-). DTI parameters were also correlated with neuropsychological (NP) measures in both groups. Methods: All participants underwent 3T MRI which included DTI at 2mm isotropic resolution and 30 diffusion directions, a comprehensive battery of NP testing, and clinical evaluation. Fractional anisotropy (FA) and mean diffusivity (MD) were determined from various regions of interest (ROIs). We analyzed group differences of FA and MD in various ROIs and conducted multivariate regressions with NP testing and DTI adjusted for age and sex. Results: 134 HIV+ patients on long-term ART with viral load of <100c/mL and 47 HIV- controls were included in this study. In the HIV+ group, compared to HIV- controls, MD was higher (more abnormal) and FA lower (also more abnormal) in various WM ROIs including the cerebral WM (MD p=0.02, FA p=0.03). However, the white matter abnormalities were not associated with worse cognition in the HIV+ group (p=0.38 for overall T-score). Instead, it was the grey matter abnormalities that were associated with worse cognition including overall T-score (p=0.03), memory (p=0.02), and information processing (p=0.03). Conclusion: DTI detected microstructural abnormalities in numerous brain parenchymal ROIs of HIV+ compared to HIV- participants. These changes are present even despite sustained virologic suppression with long-term ART. Both WM and GM were more abnormal in the HIV+ group, with the GM abnormalities more clearly associated with current NP outcomes in this cross-sectional study. Serial MRIs and NP testing with this cohort will evaluate whether the WM abnormalities are also associated with NP outcomes in the future. Zheng Wang 1 , Yu Cheng 1 , Eric C. Seaberg 2 , James T. Becker 1 , for the Neuropsychology Working Group of the Multicenter AIDS Cohort Study 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: To control false discovery rate (FDR) in identifying cognitive impairment among individuals infected with HIV, the multivariate normative comparisons (MNC) method has been used to account for intercorrelations among cognitive domains. However, the existing MNC is for cross-sectional data and does not account for the intercorrelations among repeated visits. That is, the best predictor of future test performance is current test performance. This work developed a novel longitudinal MNC (LMNC) to classify cognitive status for individuals with multiple visits, yielding more accurate results than naïvely applying the cross-sectional MNC to each visit. Methods: Data used in this work were collected before April 2017 among MSM from the Neuropsychological (NP) Substudy of the Multicenter AIDS Cohort Study. Six cognitive domains were evaluated bi-/semi-annually among these men: learning, memory, executive functioning, working memory & attention, motor speed & coordination, and speed of information processing. The final analysis included data from 22,900 visits by 3,701 men (mean age 34.9, 55.0% HIV+, mean 6.2 visits, mean follow-up 8.3 yrs) with complete data from all 6 domains. T-scores, at every domain, were adjusted for race, age, education and number of tests. HIV- men without comorbidities (n=922) were treated as healthy controls, and the LMNC was used to classify cognitive impairment among HIV- and HIV+men. Also, the cross-sectional MNC was applied to each visit with and without Benjamini-Hochberg (BH) corrections. Results: Among healthy controls the LMNC identified 5.5%with cognitive impairment. This suggests that the LMNC guarded FDR at the pre-determined 5% level. With the cross-sectional MNC applied with and without the BH correction, impairment rates were 19.8% and 9.5% in the healthy controls, respectively. In the HIV+ group, 7.3%men were identified as impaired with the LMNC, compared with 16.4% and 29.5% using the MNC method (with and

without the BH correction). In the HIV- group, the rates are 9.3%, 11.7% and 24.1%, respectively. The rates of impairment and mean T-scores across visits did not differ between the HIV- and HIV+men. Conclusion: This newly developed LMNC successfully controlled the FDR at the pre-specified level across study visits. This means that the estimates of impairment over repeated testing is more accurate than simply applying cross- sectional criteria multiple times. Corrilynn O. Hileman 1 , Sausan Azzam 2 , Kunling Wu 3 , Katherine Tassiopoulos 3 , Roger Bedimo 4 , Ronald J. Ellis 5 , Kristine M. Erlandson 6 , Asha R. Kallianpur 7 , Susan L. Koletar 8 , Alan Landay 9 , Frank J. Palella 10 , Muralidhar Pallaki 11 , Babafemi Taiwo 10 , Charles L. Hoppel 2 , Robert Kalayjian 1 1 MetroHealth Medical Center, Cleveland, OH, USA, 2 Case Western Reserve University, Cleveland, OH, USA, 3 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 4 VA North Texas Health Care Center, Dallas, TX, USA, 5 University of California San Diego, San Diego, CA, USA, 6 University of Colorado Denver, Denver, CO, USA, 7 Cleveland Clinic, Cleveland, OH, USA, 8 The Ohio State University, Columbus, OH, USA, 9 Rush University, Chicago, IL, USA, 10 Northwestern University, Chicago, IL, USA, 11 Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA Background: Neurocognitive impairment (NCI) is associated with monocyte activation, implicating a role for neuroinflammation. Activated macrophages increase glycolysis and accumulate the tricarboxylic acid (TCA) metabolites citrate and succinate, which may promote disease by engaging diverse cellular pro-inflammatory pathways or may be markers of mitochondrial dysfunction. We hypothesized that this metabolic shift contributes to NCI and frailty in people with HIV (PWH). Methods: Fasting plasma citrate and succinate were quantified at entry by liquid chromatography/mass spectrometry in AIDS Clinical Trials Group HIV Infection, Aging, and Immune Function Long-Term Observational (HAILO) study participants. Adjusting for clinically relevant variables, logistic regression and proportional hazard models examined associations of these TCA metabolites with prevalent and incident NCI, respectively; repeated measures analyses examined associations with neuropsychologic testing (NPZ-4) and 4-meter gait speed, a feature of frailty, over time. Results: 376 participants were included (276 without NCI; 100 with NCI at entry). Participants with NCI were more likely to be Hispanic (35% vs 20%; p=0.01), have less education (p<0.001) and shorter antiretroviral therapy (ART) duration (p<0.01). Overall, median age was 51 (range 40-77) yrs; 81%were male; 60% were current or former smokers. Median entry and nadir CD4 counts were 613 (IQR 449-825) and 203 (68-317) cells/mm 3 , respectively; 93% had HIV RNA <50 copies/ml. Age modified citrate associations with: prevalent NCI (figure); NPZ-4 scores and gait speed over time (p<0.01, p=0.02 and p=0.04, respectively, for interaction with age). In the oldest age-quartile (ages 56-78; n=96) each 1 SD increase in citrate was associated with a 2.4 (95% CI 1.3, 4.2) increased odds of prevalent NCI; -0.17 SD (-0.28, -0.07) lower NPZ-4 scores over time; and 0.22 second [0.12, 0.31] slower gait speeds over time. Interactions between succinate and age were not significant, but the strength of the succinate association with NCI increased with age (figure). Further, in the oldest age-quartile, each 1 SD increase in succinate was associated with a 1.9-fold (1.1, 3.9) increased hazard of incident NCI and -0.24 SD (-0.47, -0.02) lower NPZ-4 scores over time. Conclusion: The identified associations suggest common pathways in the pathogenesis of NCI and gait speed, involving mitochondrial dysfunction or inflammation, to which older PWH appear more susceptible.

402 PLASMA CITRATE AND SUCCINATE PREDICT NEUROCOGNITIVE IMPAIRMENT IN OLDER PWH

Poster Abstracts

401 COGNITIVE IMPAIRMENT AMONG HIV-INFECTED MEN WITH LONGITUDINAL FOLLOW-UP

CROI 2020 139