CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: We analyzed structural Magnetic Resonance Imaging (sMRI) data from 610 participants: 244 persons without HIV (PWoH) and 366 PWH. Freesurfer-derived region of interest (ROI) volumes were input to a machine learning technique termed HYDRA (Heterogeneity through Discriminative Analysis) to identify homogeneous patient subgroups. HYDRA clusters cases based on differences from controls, accounting for confounders such as age, sex, and race. The optimal clustering solution was determined by varying the number of clusters from 2 to 8 over 100 realizations of 10-fold cross-validation. The solution with the highest adjusted Rand index (ARI) was selected for further analysis. We then examined subtype differences in demographics, clinical measures, cognition, and imaging features (i.e., ROI volumes, resting state functional connectivity (RSFC), and cortical thickness). Demographic differences were assessed with analysis of variance and t-tests. Clinical, cognitive, and imaging differences were assessed using regression, controlling for age, sex, and race. Global Deficit Scores (GDS) were calculated by averaging cognitive domain deficit scores. Results: We identified 3 reproducible subtypes (ARI=0.42): Cluster 1 (N=103; 78.6% male), Cluster 2 (N=93; 78.5% male) and Cluster 3 (N=170; 76.5% male). Cluster 1 displayed atrophy in the lateral occipital and paracentral regions, with increased corpus callosum volume (p<0.0001) compared to PWoH. Cluster 2 had widespread cortical volumetric increases, while Cluster 3 exhibited widespread cortical and subcortical atrophy and enlarged ventricles. Similar patterns were observed in cortical thickness. Cluster 3 had significantly reduced RSFC within the dorsal attention network compared to Cluster 2. Importantly, clusters differed in clinical and cognitive aspects. PWH in Cluster 2 had a significantly lower nadir CD4 count, while Cluster 3 had the highest viral load, lowest psychomotor speed, and highest (worst) GDS. Conclusions: The identification of neurobiologically grounded biotypes of PWH may facilitate clinical trial enrichment and stratification, as well as uncover actionable features to guide development of targeted treatments. Preliminary Analysis of Longitudinal Synaptic Density Change in Virally Suppressed People With HIV Phillip Chan, Nakul Raval, Mika Naganawa, Jennifer Chiarella, Allison Nelson, Henry Huang, Lindsay S. McAlpine, Shelli Farhadian, Richard Carson, Ansel Hillmer, Serena Spudich Yale University, New Haven, CT, USA Background: Cerebral synaptic degeneration is a key pathological feature of cognitive impairment in people with HIV (PWH) on antiretroviral therapy (ART). Synaptic vesicle protein 2A (SV2A) positron emission tomography (PET) can non invasively assess in vivo synaptic density (SD). In a prior cross-sectional study, PWH on stable ART showed lower SV2A binding and thus lower SD in multiple grey matter (GM) regions of interest (ROIs) compared to people without HIV (PWoH). This preliminary analysis examines longitudinal SD changes in the PWH group of that study. Methods: PWH on suppressive ART underwent SV2A PET with [11C]UCB-J ligand, 2.7 (IQR 2.6-2.9) years apart, using a Siemens HRRT scanner. SD was determined by the non-displaceable binding potential (BPND) of [11C]UCB-J in GM ROIs, using the simplified reference tissue model 2 (SRTM2). The centrum semiovale and frontostriatothalamic area (FST) were used as the reference tissue and primary ROI. Longitudinal BPND change (∆BPND) at the ROIs, defined by the fractional change between the two scans (i.e., (2nd BPND – 1st BPND) / 1st BPND), and its potential clinical correlates, were analysed using non parametric tests. Results: Participants included 8 PWH (all male, median age 56 (IQR 53-59) years) who have been on 22 (IQR 11-24) years of ART. At the 1st scan, their CD4+ and CD8+ T-cell counts were 631 (IQR 412-831) and 576 (IQR 442-840) cells/mm 3 , respectively. Median BPND in the FST declined between the two scans (∆BPND -11 (IQR -26 to -4)%, p=0.012), as well as in other GM ROIs including frontal, occipital, hippocampus, pallidum, and cerebellum (p≤0.036), with a trend in parietal and temporal GM (p=0.069). The median ∆BPND across ROIs ranged from -7% in the parietal and temporal cortices to -18% in the pallidum ( Table ). In univariate analysis, CD4+ & CD8+ T-cell counts, CD4/CD8 ratio, duration of HIV and ART, body mass index, education years, smoking, and substance or alcohol use disorder at the 1st scan were not associated with ∆BPND in FST. Lower CD4/CD8 ratio was associated with greater BPND decline in hippocampus The figure, table, or graphic for this abstract has been removed.

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The Effects of Depression and Antidepressants on Cognition and Brain Volume in PWH and PWoH Sophie A. Sims, Beau Ances, Kalen J. Petersen, June Roman, Sarah Cooley Washington University in St. Louis, St Louis, MO, USA Background: A high rate of depression is seen in persons with HIV (PWH) and may contribute to cognitive impairment (CI) and reductions in brain volume. However, there are gaps in research on the relationship of depression severity and prescribed anti-depressants on CI and brain volumetrics in PWH. We compared the relationship between cognition and brain volume and severity of depression in PWH and persons without HIV (PWoH) and the potential effects of anti-depressants. Methods: A total of 353 PWH (with an undetectable viral load of <200 copies/mL) and 302 PWoH, from a single site were evaluated. All participants completed a full cognitive battery, questionnaires, and structural magnetic resonance imaging (MRI). Brain volumes were evaluated using Freesurfer 5.3 with particular focus on structures commonly affected by depression: frontal lobe (FLV), amygdala, and hippocampus. Raw cognitive test scores were converted into demographically-adjusted Z-scores for five cognitive domains: Learning, Delayed Recall, Executive Functioning (EF), Psychomotor (PM), and Language. Depression was measured using the BDI-ii scale and anti-depressants were recorded at study visit. Results: A greater proportion of the PWH were male, older, had less education, and were African American compared to PWoH (p’s <0.05). Overall, PWH had a significantly higher rate of depressive symptoms compared to PWoH (p<0.05). Within PWH, a higher BDI score was associated with worse performance in each of the cognitive domains except Delay Recall, while PWoH only had negative associations between BDI and EF or PM (Figure 1A). In a model that included all participants, neither FLV, amygdala, nor hippocampus volumes showed association with BDI scores. In general, a greater proportion of depressed PWH were on anti-depressants medications compared to depressed PWoH (p<0.05). Those PWH on anti-depressants had significantly smaller FLVs (Figure 1B). There was no effect of anti-depressants on cognitive performance in PWH. Conclusions: PWH have a higher prevalence of depressive symptoms compared to PWoH. Those PWH with higher depression scores had worse cognitive performance and smaller FLV. Within PWH, a higher proportion of PWH who were depressed were on anti-depressants. Furthermore, PWH who were depressed and on antidepressants had significantly smaller brain volumes but not cognitive performance. This data highlights a need for higher attention to depression and depression medications due to their negative effects on brain volumes. Analyzing Neuroanatomical Heterogeneity in HIV-Associated Cognitive Impairment Audrey Chun, Sarah Cooley, Gordon Zhaoqi An, Beau Ances, Aristeidis Sotiras Washington University in St Louis, St Louis, MO, USA Background: Central Nervous System (CNS) complications among people living with HIV (PWH) are common, but treatments remain elusive, likely due to underlying heterogeneity. Here, we aim to characterize neurobiological heterogeneity in PWH by leveraging machine learning and neuroimaging data in a large, well-characterized cohort. The figure, table, or graphic for this abstract has been removed.

Poster Abstracts

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