CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

598

High Plasma GFAP in Older PWH With Low Nadir CD4 Supports Legacy Brain Injury and Reactive Gliosis Martina Strano 1 , Federica Marmondi 2 , Sara Diotallevi 2 , Simona Bossolasco 2 , Angelo Roberto Raccagni 1 , Antonella Castagna 1 , Gabriella Scarlatti 2 , Matteo Bonato 3 , Paola Cinque 2 1 San Raffaele Vita-Salute University, Milan, Italy, 2 San Raffaele Scientific Institute, Milan, Italy, 3 University of Milan, Milan, Italy Background: Measuring cerebrospinal or plasma levels of brain injury markers may provide useful information on HIV neuropathogenesis and help characterize cognitive impairment in PWH. We compared plasma levels of these markers to cognitive function, physical performance and history of HIV in PWH≥50 years Methods: 102 ART-treated PWH ≥50 years and 40 age-matched controls without HIV infection were prospectively assessed for Neurofilament Light Chain (NFL), Glial Fibrillar Acid Protein (GFAP), Tau and Ubiquitin C-terminal hydrolase-L1 (UCH-L1) by Simoa Human Neurology 4-Plex. PWH were evaluated for neurocognitive performance [TMT-A, TMT-B, Digit Symbol (DS)], depression and anxiety (Hospital Anxiety and Depression scale), physical function (handgrip, chair-stand test for muscle strength, mini-BEST test for balance and mobility), current and nadir CD4+ counts and years of HIV infection. Values are shown as median (IQR); group comparisons were analysed by Mann-Whitney test and correlations by Spearman's correlation test and linear regression Results: No significant differences between PWH and controls were observed for age [60 (57-63) vs. 57 (52-62)] and any of the four markers [NFL: 11.5 (8.2 16.5) vs. 10.6 pg/µL (9.4-14.3); GFAP: 108.3 (76.2-144.2) vs. 95.4 (76.5-138.7); Tau: 2.69 (1.88-4.30) vs. 3.30 pg/mL (2.24-4.89); UCH-L1: 18.7 (10.6-28.8) vs. 19.5 pg/mL (11.4-34.2)]. In PWH, NFL and GFAP were highly correlated (p=0.0002, r=0.356); higher NFL and GFAP correlated to older age (both p<0.0001, r=0.356 and 0.496, respectively) and GFAP levels were higher in women (p=0.01); higher NFL was associated with lower performance at mini-BEST test (p<0.0001, r=-0.334), and higher GFAP with lower performance at DS (p=0.043, r=-0.201), handgrip (p=0.0001, r=-.0367) and mini-BEST test (p=0.015, r=-0.239), lower nadir CD4+ counts (p=0.0004, r=-0.343) and longer duration of infection (p=0.045, r=0.199). By multivariate analysis (Table), higher NFL levels were associated with older age and better performance at the Mini-BEST test; higher GFAP with older age, female gender and low nadir CD4+ count. Conclusion: Beyond the expected correlation of higher GFAP and NFL with age, the specific association of high GFAP level with low nadir CD4+ counts and long infection duration may reflect a legacy injury with reactive gliosis, of a previous untreated CNS HIV infection. Practically, physical performance may help define the functional status associated with elevated markers of CNS cell injury

group in a generalized additive mixed model. Education, ethnicity, sex, and time since first cognitive test were included as covariates. Results: A total of 679 participants (279 PWoH, mean (standard deviation) age 40 (17) years old; 305 PWHU, age 49 (14) years old; 95 PWHD, age 40 (17) years old), tested up to 6 times for a total of 968 data points, were analyzed. Age was associated with cognition in each group, with cognition worsening with increasing age. The overall effect significantly differed between all groups (PWoH > PWHU > PWHD). The shape of the age-cognition relationship was identical for PWoH and PWHU, only significantly shifted downward. Shape significantly differed in PWHD, resulting in a steeper, steadier decline in cognition with increasing age relative to PWoH and PWHU. Conclusion: While there is a decrease in cognition associated with HIV, the age-cognition relationship mirrors PWoH when virologically controlled. Older, uncontrolled PWH are at greater risk for cognitive decline and should be the focus of future studies.

600

Hepcidin Modifies Effects of Age and Erythrocyte Indices on Cognitive Function in People With HIV Azin Tavasoli 1 , Oluwakemi K. Okwuegbuna 2 , Jennifer E. Iudicello 1 , Asha Kallianpur 3 , Ronald J. Ellis 1 , Scott L. Letendre 1 1 University of California San Diego, La Jolla, CA, USA, 2 Khure Health, Toronto, Canada, 3 Case Western Reserve University, Cleveland, OH, USA Background: Cognitive impairment (CI) in people with HIV (PWH) is associated with abnormal erythrocyte indices, which may result from inflammation, disturbed iron metabolism, and other factors. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are indices of erythrocyte volume and hemoglobinization, which help to classify anemia. Erythropoiesis requires bioavailable iron, levels of which are regulated by a complex system of peptide hormones, including the acute-phase peptide, hepcidin. Methods: Iron biomarkers (hepcidin, erythropoietin, ferritin, erythroferrone, total iron-binding capacity, soluble transferrin receptor) and erythrocyte indices were quantified using commercial assays in 88 virally suppressed antiretroviral therapy (ART) treated PWH. All participants underwent comprehensive cognitive testing, and their performance was summarized by T-scores. Multivariable regression analysis of cognitive performance was performed using the Akaike Information Criterion and backward selection. Results: Participants were mostly middle-aged (mean age 44 years), white (52.3%), and men (84.1%). Hepcidin levels were detectable (>1.0 ng/mL) in 42 (47.7%) and modified the relationship between global T-score and either age (interaction p-value=0.0072) or MCV (interaction p-value=0.0185). Stratified analyses identified that lower global T-scores were associated with older age (p=0.001) or higher MCV (p=0.0046) only when hepcidin was undetectable. A similar analysis was performed to assess interactions between anemia and iron indices in relation to global T-scores and this identified statistically significant interactions between anemia and either MCV (p=0.0119) or MCH (p=0.0127). Stratified analyses identified that lower global T-scores were associated with higher MCV (p=0.0015), and higher MCH (p=0.0026) only among anemic participants. These associations remained statistically significant after adjustment for sex, race, ethnicity, duration of HIV infection, CD4+ T-cell count and nadir, duration of ART, and HCV serostatus. Conclusion: These findings suggest that a combination of iron-related (hepcidin, MCH) and iron-unrelated (age, higher MCV) mechanisms influence cognitive health. While these cross-sectional results require confirmation in larger, longitudinal studies with more women, they highlight hepcidin as a potential modifying factor in associations of age and erythrocyte indices in relation to cognitive performance in PWH.

Poster Abstracts

599

Pattern of Age-Related Cognitive Decline in People With HIV Depends on Viral Suppression James T Kennedy , Sarah Cooley, Beau Ances Washington University in St Louis, St Louis, MO, USA Background: The introduction of combination anti-retroviral therapy (cART) has led to increased life expectancy of persons living with HIV (PWH) and a reduction in the prevalence of HIV-associated neurocognitive disorder. As PWH grow older, it is important to understand the cognitive trajectories of PWH compared to people without HIV (PWoH) and how treatment efficacy impacts age related cognitive changes. Methods: PWoH and PWH (virally undetectable; viral load ≤50/ml, PWHU; and detectable; PWHD) were recruited and repeatedly administered a simple cognitive battery – Category Fluency (language), Hopkins Verbal Learning Test (learning subtest), Trails A (psychomotor/processing speed), and Trails B (executive function) – that were combined to form a composite (NPZ4). The composite was formed by normalizing scores to baseline performance (flipping timed tests so that lower values means poorer performance), and averaging Z-scores. The association between cognition and age was assessed for each

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