CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

duration was 18.7 years (IQR: 15.3–21.0), and 61.2% had cognitive impairment. There was no significant difference in the proportion of PWH with cognitive impairment at baseline between those in Q4 and those in Q1–3 of p-tau217. However, PWH in Q4 were significantly more likely to have a reduction in MoCA score at follow-up visit than those in Q1–3 (62.5% vs. 49.2%, P =0.01). In the adjusted model, PWH in Q4 showed a significantly greater decline in cognitive performance, with a MoCA score decrease of -4.3 (95% CI -5.8 to -2.7) compared to -1.7 (95% CI -2.6 to -0.8) for Q1–Q3 from age 50 to 80 years ( Figure ). The association between higher p-tau217 levels (Q4 vs. Q1-Q3) and greater decline in MoCA scores become more pronounced with increasing age ( P -interaction=0.02). Conclusions: Older virologically suppressed Thai PWH with higher baseline p-tau217 levels showed a greater cognitive decline. Measurements of biomarkers for staging and prognostication of AD are ongoing. Semaglutide Improves Cognitive Function in HIV, Effect Mediated by Decrease in Inflammation Ornina Atieh 1 , Jhony Baissary 1 , Qian Wu 1 , Abdus Sattar 1 , Danielle Labbato 2 , Allison Ross Eckard 3 , Christian Mouchati 4 , Grace A. McComsey 1 1 Case Western Reserve University, Cleveland, OH, USA, 2 University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 3 Medical University of South Carolina, Charleston, SC, USA, 4 University of Connecticut Health Center, Farmington, CT, USA Background: People with HIV (PWH) are at higher risk for visceral adiposity and enhanced inflammation, and lower neurocognitive function when compared to controls without HIV. In a recent randomized placebo-controlled clinical trial of the GLP1 receptor agonist semaglutide, we demonstrated that PWH with lipohypertrophy had a decrease in weight, visceral adipose tissue, and in several inflammatory markers including high sensitivity C-reactive protein (hs-CRP). This study aims to investigate the effect of semaglutide on neurocognitive function and the mediation of this effect by changes in adiposity and inflammatory markers in PWH. Methods: This study is a randomized, double-blind, placebo-controlled phase 2b clinical trial conducted at University Hospitals of Cleveland, Ohio. We included adult PWH on ART with controlled HIV, BMI of ≥25 Kg/m 2 , and increased waist-to-hip ratio. Participants were randomized 1:1 to receive 32 weeks of subcutaneous Semaglutide or placebo. The Cognivue®, an FDA approved computer-based test, was used to evaluate cognitive function at baseline and at 32 weeks. This comprehensive assessment encompassed multiple subdomains, including memory, visuospatial ability, attention, and executive function. Furthermore, a whole-body DEXA scan and a non-contrast helical CT scan were used to assess for changes in body composition, alongside the evaluation of inflammatory markers. We performed causal mediation analysis in examining association among various direct and indirect effects of semaglutide on the cognitive scores. Results: 108 participants were included (54 per arm); 62% non-white, 40% female, and median age of 53 years. Compared to placebo, PWH on semaglutide

in hs-CRP levels (p=0.04). No correlations were observed between changes in cognitive scores on semaglutide and changes in total or central adiposity. Conclusions: Semaglutide has shown a beneficial impact on cognitive function in people with HIV, particularly in relation to visuospatial cognitive function. This effect appears to be mediated by the effect of the drug on inflammation. Brain Gray and White Matter Alterations in Cognitive Long COVID Lindsay S. McAlpine 1 , Nuno Barros 2 , Allison Nelson 1 , Rafay Khan 2 , Cheryl Lacadie 1 , Background: Cognitive dysfunction is a common symptom of Long COVID (LC), but its underlying pathobiology is unclear. We hypothesized that multimodal structural brain MRI imaging in people with cognitive LC (c-LC) would demonstrate grey and white matter alterations in brain regions relevant to c-LC symptoms compared to no LC (n-LC) controls. Methods: Individuals with c-LC (new self-reported cognitive symptoms >3 months after COVID) and n-LC (COVID >3 months prior and no LC) were prospectively enrolled for studies on a single Siemens 3T scanner. Sequences included 3D T1 MPRAGE (1mm) for cortical gray matter (CGM) volume, 3D FLAIR (1.2mm) for white matter hyperintensity (WMH) volume, and Diffusion Tensor Imaging (DTI) (2mm) for white matter integrity measures fractional anisotropy (FA) and mean diffusivity (MD). Post-processing used Icometrix AI-based software and Bioimage Suite. The Johns Hopkins atlas was used to generate FA and MD for regions of interest (ROI). Analyses used parametric statistics and FDR to correct for multiple comparisons. Results: 23 c-LC (median age 45 years [IQR 41–59], 73% female, 630 days [IQR 365–829] after COVID-19) and 19 n-LC (median age 38 [33 – 44], 73% female, 516 days [IQR 410-797]) were enrolled. The groups differed in age (p=0.03) but were similar in gender, race, and cardiovascular risk factors which were low in prevalence. CGM volumes were lower in the c-LC group in three key regions: right parietal lobe and supramarginal region (SM), right ventrolateral prefrontal cortex (VLPFC), and left posterior cingulate (for statistics, see Table). WMH lesion volume was similar between groups (c-LC: 0.65 mL n-LC: 0.65 p:0.90). In the fornix, FA and MD were both altered in the c-LC group compared to n-LC. In the c-LC group, MD was lower in the left posterior corona radiata and transverse pontine fibers compared to n-LC (Table). There was no difference between groups in the remaining ROIs. Conclusions: Our finding of specific regional grey and white matter alterations aligns closely with c-LC symptomatology. The SM is intimately connected to the VLPFC and is involved in articulatory sequencing and language and executive processing; VLPFC is involved in speech production and emotional associations Shelli Farhadian 1 , Todd Constable 1 , Serena Spudich 1 1 Yale University, New Haven, CT, USA, 2 Icometrix, Leuven, Belgium

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and regulation. Altered CGM in the left cingulate and left corona radiata and DTI measures in the fornix aligns with dysfunction of key memory circuits. These structural 3T brain MRI findings may serve as biomarkers for diagnostic and mechanistic understanding of c-LC.

had a significant increase in visuospatial, naming/language, and delayed recall scores at 32 weeks (p = 0.01, 0.05, and 0.04, respectively). After adjusting for sex and CD4 count, only the visuospatial score remained statistically significant (p=0.05). The total natural direct effect (TNDE) of semaglutide maintained a positive effect on the visuospatial score while accounting for potential changes

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CROI 2025