CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: The new humanized glia mouse mirrors HIV brain disease as seen in humans with significant neuropathological, behavioral, and brain structural changes that persist even with ART. Thus, this model is the best platform to study HIV neuropathology, viral reservoirs and to develop therapeutic strategies. Evaluating White Matter Integrity in Relation to HIV Severity and Cognitive Impairment Owen Guo, Kalen J. Petersen, Sarah Cooley, Babatunde Adeyemo, Beau Ances, Jeremy Strain Washington University in St Louis, St Louis, MO, USA Background: Though incurable, HIV has become widely treatable with combination antiretroviral therapy (cART), significantly extending the lifespan of people living with HIV (PLWH). This has resulted in an aging PLWH population facing growing concerns for age-associated HIV comorbidities such as cognitive impairment (CI), which remains equally prevalent and relevant for PLWH in the cART era. The mechanisms connecting HIV and CI are unknown, though HIV is associated with reduced white matter (WM) integrity. Additionally, previous studies often have not separated PLWH into those with undetectable and detectable viral loads. Here, we investigate WM integrity's relation to HIV severity and CI status using diffusion tensor imaging (DTI). Methods: HIV severity was obtained through viral load measurements, and CI status was obtained through neuropsychological testing. Brain imaging data was processed following the diffusion processing pipeline provided by the FMRIB Software Library (FSL). We generated scalar maps for four different DTI metrics using tract-based spatial statistics (TBSS). T-tests were compared between controls and HIV individuals with or without viral suppression on whole-brain voxel-wise group statistics using FSL's randomise function. All analyses incorporated age and gender as covariates and corrected for multiple comparisons. Results: A total of 111 non-HIV participants and 193 HIV individuals were included into this study with 54 showing detectable levels of viral load. The results showed a statistically significant decrease in WM integrity via decreased fractional anisotropy for detectable and undetectable groups compared to control groups (p<0.05 corrected). Additionally, elevated diffusion was present for individuals with detectable viral loads compared to undetected for mean diffusivity (p<0.05 corrected) and elevated radial diffusivity compared to controls (p<0.05 corrected). No significant findings in white matter decline were observed when comparing between groups based on cognitive impairment. Conclusions: This study evaluated a large cohort of HIV individuals with and without viral load suppression on metrics of white matter integrity. These findings suggest that WM integrity may worsen with increasing HIV severity with increased demyelination for individuals with detectable levels of viral load. However, no association was found between HIV severity and CI status, indicating a need for further investigation into their mechanistic link. The figure, table, or graphic for this abstract has been removed. Interaction Between Age, Brain Volume, and HIV Status in Predicting Cognition James T. Kennedy, Sarah Cooley, Kalen J. Petersen, Beau Ances Washington University in St Louis, St Louis, MO, USA Background: Aging and HIV infection are independently associated with worse cognitive performance and decreased brain volume. It is unknown if the relationship between brain volumes, cognition, and aging differs in people with HIV (PWH) relative to people without HIV (PWoH) or if poor viral suppression affects these relationships. Methods: Cognitive tests and T1 MRI scans were collected in PWoH and PWH from the St. Louis area from ongoing longitudinal studies. PWH were split into undetectable (≤50 viral load/ml; PWHU) and detectable (PWHD). Four cognitive tests (Category Fluency, Hopkins Verbal Learning Test – Learning scale, Trails A, and Trails B) were administered. Performance was converted to an uncorrected Z-score and averaged (reversing timed tests) to form a cognitive composite. Scans were processed through FreeSurfer 5.3 to generate regional brain volumes corrected for intracranial volume. Nonlinear age (A), regional brain volume (V), cognition (C), and HIV group (H) relationships (C~AxH, V~AxH, C~VxH, and C~AxVxH) were explored using generalized additive mixed models. ID was treated as a random variable and sex, education, scanner, and time

since baseline as parametric. We applied a false discovery rate correction for significance at p<.05. Results: Participants consisted of 259 PWoH, 260 PWHU, and 84 PWHD who had 841 total sessions. The sample was 71% male and 68% African American with a mean baseline age of 40.2 years old and 13.5 years of education. The cognitive composite significantly differed amongst all groups (PWoH>PWHU>PWHD), brain volumes were larger in PWoH relative to PWH in most regions; PWHU had greater volumes than PWHD in the lateral orbital frontal cortex, superior temporal, precuneus, and putamen. For both PWoH and PWH, cognition, age, and volume were significantly associated with each other. Slopes were identical for PWoH and PWHU across analyses but significantly differed compared to PWHD for age and cognition, cognition and volume, age and volume in the lentiform, and for the interaction of age, volume, and cognition. Slope interaction analyses found that low volumes at older ages were more deleterious to cognitive function in PWHD compared to PWHU or PWoH. Conclusions: HIV legacy effects are observed for cognition and brain volume, with similar aging trajectories for PWHU and PWoH. Detectable viral load was associated with steeper aging slopes for cognition and lentiform volume. Lower brain volumes at older ages contributed to poor cognitive performance in PWHD only. Plasma Inflammation Is Associated With Brain Cellularity in Diffusion Based Spectral Imaging in HIV Advika Srinivas 1 , Sarah Cooley 1 , Jeremy Strain 1 , Tricia Burdo 2 , Stephen Baak 3 , Julie Wisch 1 , Sheng-Kwei Song 1 , Beau Ances 1 1 Washington University in St Louis, St Louis, MO, USA, 2 Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA, 3 Rutgers University, Piscataway, NJ, USA Background: Elevated levels of inflammation and neurodegeneration in the brain and periphery are associated with worse brain health outcomes in persons without HIV (PWoH). People with HIV (PWH) may have greater peripheral inflammation and neurodegeneration that may cause elevated brain inflammation and white matter changes. Brain inflammation can be measured using diffusion-based spectral imaging (DBSI) derived global cellularity (GC) which is associated with activated microglia. This study examines the association between plasma measures of inflammation and neurodegeneration and brain measures of inflammation in PWH. Methods: 227 PWH (77% male) and 45 PWoH (56% male) age≥30 underwent brain imaging and blood draw for inflammatory and neurodegeneration markers. The isotropic portion of the diffusion weighted signal attributed to cellularity was extracted globally and processed using established pipelines. Plasma (sCD163, sCD14, glial fibrillary acidic protein [GFAP], and neurofilament light chain [NfL]) biomarkers were quantified. CD14+CD16-, CD14+CD16+ and CD14-CD16+ monocyte cell populations were also quantified. GC was first compared with age. GC was then compared to plasma markers and monocytes using regression models with age and sex included as covariates. Results: PWH had a significantly higher GC (p<0.001) than PWoH. Increasing age was significantly associated with increased GC in PWH (p<0.001) but not PWoH. Higher plasma sCD163 was associated with lower GC (p<0.05) in PWH. In PWoH, elevated CD14+CD16+ monocytes were associated with lower GC (p<0.001) while elevated plasma sCD163 was associated with higher GC (p<0.01). Both plasma GFAP and NfL were not associated with any changes in GC. Conclusions: Altered levels of plasma inflammatory marker sCD163 and inflammatory CD14+CD16+ monocytes were associated with changes in brain inflammation in PWH and PWoH. However, plasma markers of neurodegeneration (NfL and GFAP) showed no association with central inflammation. The results for PWH align with the CD14+CD16+ monocytes being inflammatory and the sCD163 being anti-inflammatory while the results in PWoH display opposite trends. This suggests that DBSI GC may be sensitive to detecting central inflammatory processes happening specifically in PWH, but not PWoH. This could also suggest that plasma sCD163 and CD14+CD16+ monocytes may have different inflammatory process in PWH than PWoH. Peripheral markers of inflammation and monocytes may provide better insight into or predict brain inflammation in PWH. The figure, table, or graphic for this abstract has been removed.

590

592

Poster Abstracts

591

CROI 2025 158