CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

602

Higher suPAR Relates to Domain-Specific Cognitive Function in Virally Suppressed Women With HIV Hemil Gonzalez 1 , Eran F. Shorer 2 , Raha M. Dastgheyb 3 , Eunsil Hahm 1 , Yanxia Cao 1 , Kathleen M. Weber 4 , Leah H. Rubin 5 , Audrey L. French 6 , for the MACS/WIHS Combined Cohort Study (MWCCS) 1 Rush University Medical Center, Chicago, IL, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Hektoen Institute of Medicine, Chicago, IL, USA, 5 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 6 Stroger Hospital of Cook County, Chicago, IL, USA Background: Chronic inflammation plays a role in cognitive function in people with HIV (PWH). Soluble Urokinase Plasminogen Activator (suPAR) is a biomarker of chronic inflammation previously associated with cognitive impairment in a small study of men with HIV. Our study aimed to examine whether elevated suPAR levels are associated with domain-specific cognitive function in virally suppressed women with HIV (VS-WWH), potentially providing a pre-clinical indicator for cognitive complications. Methods: suPAR levels were assessed in duplicate via ELISA (ViroGates; Denmark) from stored (-80C) plasma in a sample of 188 VS-WWH (all participants had VL <200 copies/mL, 50% with impairment in ≥2 cognitive domains) participating in the Chicago Cook County site of the MACS-WIHS Combined Cohort study. Blood samples were collected between November 2004 and September 2017 at either the same visit as the cognitive assessment for 179 (95%) participants or from the visit immediately prior (within 90 days of assessment) from the remainder. Participants completed biennial cognitive testing. Cognitive domains included attention, executive function, processing speed, verbal memory, verbal learning, verbal fluency, and motor function. Domain-specific cognitive impairment was defined as demographically adjusted T-scores ≤40. Multivariable linear regression models assessed associations between log-transformed suPAR and cognitive domain T-scores adjusting for age. Results: VS-WWH had a mean age of 52, a mean CD4 of 693, 72% were Black, and 67% had completed high school education. The mean suPAR level was 3.23 ng/mL (variation coefficient 56.8%). Higher log suPAR levels were associated with poorer processing speed (β=-0.18, 95%CI -0.31, -0.04, P =0.01), verbal learning (β=-0.15, 95%CI -0.29, -0.02, P =0.029), verbal fluency (β=-0.14, 95%CI -0.27, -0.01, P =0.038), and motor function (β=-0.13, 95%CI -0.26, -0.00, P =0.045)(see Table ). There were no associations with other cognitive domains. Conclusions: These findings suggest that suPAR offers potential as an indirect biomarker for systemic chronic inflammation, verbal abilities, and psychomotor speed in this population. Although the effect sizes were small, further exploration of this molecule is warranted as it may be helpful as part of a larger pre-clinical predictive model of cognitive changes in this population. Elucidating the mechanisms of suPAR production in this context will contribute to our overall understanding of its applicability.

(p=.009; 95%CI -4.904-0.704), male sex (p=.011; 95%CI -40.852-5.336) and HIV acquisition at birth (p<.001; 95%CI 36.643-135.900) of GFAP; and higher GFAP (p=.014, 95%CI 0.014-0.122) of UCH-L1. Conclusions: Plasma CNS tissue marker levels do not support higher CNS injury risk in HTE-PWH. Several other variables seem independently and variably associated with higher levels of each marker. Comprehensive Study of CSF Fluid β2-Microglobulin, a Marker of CNS Immune Activation in HIV Birgitta Anesten 1 , Henrik Zetterberg 1 , Staffan Nilsson 1 , Magnus Gisslén 1 , Aylin Yilmaz 2 1 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, 2 University of Gothenburg, Gothenburg, Sweden Background: HIV-1 invades the central nervous system (CNS) during acute infection and thereafter persists in the CNS. This leads to chronic intrathecal immune activation which can be measured by various biomarkers in cerebrospinal fluid (CSF). β 2 -microglobulin (β 2 M) is a marker of cellular immune activation that has previously been studied in CSF in people with HIV (PWH), but mainly in smaller cohorts. The aim of this study was to describe CSF β 2 M levels in a large cohort of PWH. Methods: In this retrospective study, we determined levels of β 2 M, neopterin, HIV RNA, albumin ratio, IgG index, CD4 + T cell count, neurofilament light chain protein (NfL), and leukocyte counts (WBC), in CSF and blood in PWH with and without ART. Participants were divided into seven groups: 1) neuroasymptomatic HIV (NA), 2) NA CSF escape, 3) symptomatic CSF escape, 4) secondary CSF escape, 5) HIV-associated dementia (HAD), 6) opportunistic CNS infections (CNS OI), and 7) elite controllers. Results: We included 638 individuals: NA (N = 556); NA CSF escape (N = 33); symptomatic CSF escape (N = 4); secondary CSF escape (N = 5); HAD (N =16); CNS OI (N = 18); and elite controllers (N = 6). In addition, 59 HIV negative controls were included. Highest CSF β 2 M levels were found in HAD and symptomatic CSF escape (figure 1). In 112 longitudinally followed NA participants, increased CSF β 2 M levels (90%) were found at baseline, compared with 96% for CSF neopterin. After initiation of ART CSF β 2 M levels decreased by 9% per month and CSF neopterin with 16%. Still, 68% had CSF β 2 M and 80% had CSF neopterin levels above the reference values after six months. Conclusions: In this extensive cohort of PWH with various stages of disease, CSF β 2 M was shown to be a robust marker of intrathecal inflammation, with the highest levels found in HAD and in symptomatic CSF escape. ART decreases β 2 M levels, but, 68% still had increased levels after six months, despite having achieved viral suppression. The figure, table, or graphic for this abstract has been removed.

601

Poster Abstracts

CROI 2025 162