CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Regression models adjusting for age and sex were used to predict longitudinal change scores for CEN rsFC. Results: In the overall sample, CEN rsFC increased from baseline to follow-up (mean change=+13.4% ; 95% confidence interval [CI]: +2.2%, +25.1%). We detected no differences by HIV status in CEN rsFC at baseline or follow-up and no differences by HIV status in CEN rsFC change scores. Among PLWH, those infected longer at baseline (i.e., with detectable HIV antibodies and no longer in acute HIV) exhibited more negative CEN rsFC change scores (β=-0.78; 95% CI:-1.50, -0.06). Higher absolute CD4 counts at baseline predicted more positive CEN rsFC change scores (β=0.5; 95% CI:0.17, 0.83). Due to the small number of female participants, it was not possible to calculate sex-stratified effect estimates. Conclusion: In the overall sample, CEN rsFC increased over time. Among PLWH, these gains in CEN rsFC were substantially weaker among those with evidence of greater immunopathology at baseline, as indexed by lower CD4 count. Gains in CEN rsFC were weaker among those infected longer at baseline, as indicated by the presence of detectable HIV antibodies. These findings suggest that HIV related differences in CEN rsFC not yet apparent in early infection, but greater immunopathology in early infection alters early longitudinal trajectories of CEN rsFC. CD4 nadir may be an important prognostic marker for reduced CEN rsFC later in life in PLWH. Interventions that preserve CEN rsFC (e.g., non invasive neuromodulation) may protect against emergence of psychiatric and neurocognitive comorbidities in PLWH. Inflammation and Cognition Associations in Young Adults With Perinatal HIV Exposure and/or Infection Megan S. McHenry 1 , Yanling Huo 2 , Paige L. Williams 2 , Kunjal Patel 3 , Wei Li 1 , Alka Khaitan 1 , Sharon Nichols 4 , for the Pediatric HIV/AIDS Cohort Study (PHACS) Network 1 Indiana University, Indianapolis, IN, USA, 2 Harvard University, Cambridge, MA, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 University of California San Diego, La Jolla, CA, USA Background: Children with perinatal HIV exposure, particularly those with HIV infection, are at risk for worse cognitive outcomes compared to unexposed children. Inflammation is a potential risk factor for worse cognitive outcomes in populations with HIV, but no studies have evaluated this association within young adults with perinatal HIV (YAPHIV) or perinatal HIV exposure but uninfected (YAPHEU). We evaluated the association between inflammatory biomarkers and NIH Toolbox cognitive outcomes in YAPHIV and YAPHEU. Methods: Participants with available plasma samples and NIH Toolbox cognitive scores at entry into the PHACS AMP Up study were included in the analysis. Principal Component Analysis (PCA) was used to derive factor scores from biomarkers for monocyte activation (sCD14, sCD163), acute phase inflammation (CRP, fibrinogen, TNF-α), proinflammatory/Th1/Th17 (IFN-γ , IL-1β, IL-2, IL-12p70, IL-17a), or anti-inflammatory/Th2 (IL-4, IL-6, IL-10) cytokines and homeostasis (GM-CSF, Fractalkine). We computed Pearson correlations of individual log-transformed biomarkers and four PCA factors with Composite Standard Scores for Total (TC), Fluid (FC; e.g., processing speed, executive functions), and Crystallized Cognition (CC; e.g., word knowledge), separately by HIV status. Results: 638 participants (YAPHIV: n=521, mean age 22.7 (SD:4.2) years; YAPHEU: n=117, mean age 19.0 (SD:1.4) years) were included. Mean TC, FC, and CC were similar for YAPHIV and YAPHEU. Compared to YAPHEU, YAPHIV had higher levels of TNF-α, sCD14 and sCD163 and lower levels of IL-2, IL-4, IL-6, IL-10, IL-1β, IL-12p70, IL-17a, Fractalkine, and GM-CSF. YAPHIV had weak negative correlations of FC with CRP, sCD163, and Fibrinogen (r=-0.08 to -0.09) and of CC and TC with sCD163 (r=-0.09). YAPHEU had positive correlations of FC with IL-2, IL-12p70, and IL-17a (r=0.18 to 0.24) and negative correlations of CC with Fractalkine and IL-10 (r=-0.17). Factor 3 (primarily sCD14, CRP, Fibrinogen) was weakly negatively correlated with both FC and TC in YAPHIV (r=-0.10) and Factor 1 (primarily GM-CSF, Fractalkine, IL-2, IL-1β, IL-12p70, IFN-γ, IL-17a) was positively correlated with FC in YAPHEU (r=0.19) (Table). Conclusion: Cognition weakly correlated with different summary PCA factor scores in YAPHIV (monocyte and acute inflammation) and YAPHEU (Pro inflammatory/Th1/Th17 cytokines). Further research is needed to understand the role of inflammatory profiles, perinatal HIV exposure or infection and other factors in cognition.

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Pro-Inflammatory Glycomic Dysregulations Define HIV-Associated Neurocognitive Impairments Leila B Giron 1 , Janeway Granche 2 , Frank Palella 3 , Katherine Tassiopoulos 4 , Mohamed Abdel-Mohsen 1 1 Wistar Institute, Philadelphia, PA, USA, 2 Harvard TH Chan School of Public Health, Cambridge, MA, USA, 3 Northwestern University, Chicago, IL, USA, 4 Harvard TH Chan School of Public Health, Boston, MA, USA Background: In the general population, host glycomic alterations drive inflammation and precede onset of inflammation-associated diseases. However, it remains unclear whether glycomic alterations are associated with development of inflammation-associated diseases, including neurocognitive impairment, in people with HIV (PWH) on suppressive antiretroviral therapy (ART). Methods: In this analysis conducted within the ACTG A5322 (HAILO), 20 PWH on ART (10 men and 10 women) who were cognitively impaired over 8 years of follow-up were matched by sex, age, and ethnicity to 20 controls without impairment. Cognitive function was assessed using the Trail Making A and B tests, the Wechsler Adult Intelligence Scale-Revised Digit Symbol test, and the Hopkins Verbal Learning Test–Revised. NPZ4 scores, calculated as the mean of these test scores. Cognitive impairment was defined as ≥2 z-scores ≤1 SD from the mean or one z-score ≤2 SD from the mean. Longitudinal samples, collected over 8 years (5-9 per participant), were analyzed for 133 IgG and plasma glycans (using capillary electrophoresis) and 10 inflammation markers (using multiplex arrays). Longitudinal associations between neurological impairment or NPZ4 scores and glycans and inflammation markers were assessed using mixed effects models. Results: Cognitive impairment was associated with higher levels of total bisected GlcNAc glycans, as well as several glycomic traits containing bisected GlcNAc, such as (G0FB and G1FB) on IgGs, pro-inflammatory glycans that increase with age (Fig. 1A). Higher NPZ4 scores were associated with lower levels of these glycans (Fig. 1B). Consistent with their pro-inflammatory roles, these glycans, specifically G0FB, correlated with higher levels of the inflammatory marker TNFα (P<0.01; rho=0.4). Conversely, cognitive impairment was associated with lower levels, and NPZ4 scores with higher levels, of glycans that contain the anti-inflammatory sialic acid and fucose (such as FA2G2S1 and FA2G2S2). Finally, among inflammation markers, IL-10 and sCD14 exhibited positive correlations with neurocognitive impairment and negative correlations with NPZ4 scores. Conclusion: Aging- and inflammation-associated host glycomic dysregulations are linked to the presence of neurological impairments in PWH on ART. Future studies are warranted to validate these exploratory findings and to examine potential prognostic and functional significance of host glycans and inflammatory markers in the pathogenesis of neurological impairments in PWH. The figure, table, or graphic for this abstract has been removed. WITHDRAWN Immune Checkpoints in the Central Nervous System and HIV-Associated Neurocognitive Disorder Wei Li , Fahim Syed, Xiang Gao, Qigui Yu Indiana University, Indianapolis, IN, USA Background: Immune checkpoints (ICPs) exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance through their ligand-receptor interactions. ICPs exist in both membrane-bound and soluble forms in vivo. Imbalances between inhibitory and stimulatory membrane bound ICPs (mICPs) in malignant cells and immune cells in the peripheral blood and tissues have been well documented. Blockade of inhibitory mICPs such as CTLA-4, PD-1, and PD-L1 has become a revolutionary treatment for advanced stages of malignancies such as melanoma. However, the origin, regulation,

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Poster Abstracts

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CROI 2024 148