CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: HIV-1, independent of traditional risk factors and ART, is associated with a pathologic circulating EMV phenotype. Reduced NO bioavailability and impaired fibrinolytic capacity in brain endothelial cells heighten the risk and accelerated rate of ischemic stroke. EMVs represent a mechanistic factor underlying HIV-1-related cerebrovascular risk. Vascular Inflammation in Neuropsychiatric Post-Acute Sequelae of COVID-19 Lindsay S McAlpine , Hailey Reisert, Bibhuprasad Das, Allison Nelson, Jennifer Chiarella, Shelli Farhadian, Serena Spudich Yale University, New Haven, CT, USA Background: Neuropsychiatric post-acute sequelae of COVID-19 (N-PASC) include cognitive impairment, mood changes, headache, and neuropathy. Biomarkers of endothelial and platelet dysfunction are elevated in patients with acute COVID-19, but it is unknown if this persists in individuals with N-PASC. We investigated for vascular inflammation in N-PASC and controls. Methods: Participants with N-PASC (ongoing neuropsychiatric symptoms >3 months after COVID-19) and controls underwent cross sectional clinical assessment and blood collection. Plasma samples were tested via multiplex bead-based ELISA for the following analytes: a-2 macroglobulin, α1-acid glycoprotein (AGP), C-reactive protein (CRP), Fetuin A36, haptoglobin, L-selectin, platelet factor 4 (PF4), and serum amyloid protein (SAP) A (Eve Technologies). Non-parametric multiple Mann-Whitney testing was used with False Discovery Rate adjustment made to address multiple comparisons. Results: The N-PASC (N; n=40) and control (C; n=16) groups were similar in age (N: 45 years, C: 40 years, p=0.15), gender (N: 73% female, C: 69% female, p=0.76), race (N: 20% non-white, C: 37% non-white, p=0.19) and cardiovascular risk factors (diabetes, smoking, hypertension, obesity, and cardiac disease, p>0.05). The groups had similar time from acute COVID-19 to study visit (N:325 days, C:418, p=0.95). N-PASC symptoms included cognitive issues (72%), new or worsening anxiety or depression (67%), and headache (61%). Five markers were elevated in N-PASC: a-2 macroglobulin (N: 994,143 ng/mL, C: 749,109, p=0.04), CRP (N: 8,851,400 pg/mL, C: 3,625,000, p=0.01), haptoglobin (N: 194,735 ng/mL, C: 99,319, p=0.046), L-selectin (N: 808,346 pg/ mL, C: 670,940, p=0.01), and SAP (N: 6,252,000 pg/mL, C: 3,186,650, p=0.0003) (Figure). Fetuin A36 was reduced (N: 132,476 ng/mL, C: 207,355, p=0.05). There were no differences in the other biomarkers tested. Conclusion: We report key differences in vascular inflammatory plasma biomarkers in individuals with N-PASC, including elevations in plasma proteins that indicate ongoing systemic inflammation (CRP, haptoglobin, SAP), endothelial dysfunction (a-2 macroglobulin), and atherosclerosis (L-selectin, fetuin A36, SAP). These findings suggest the N-PASC population may be at risk of persistent vascular inflammation and/or atherosclerosis. Further studies should longitudinally investigate endothelial inflammation and atherosclerosis in individuals with N-PASC.

antihypertensives (0.28/yr exposure [0.13, 0.43], p<0.001), and antidepressants (1.58/yr exposure [0.02, 3.13], p=0.047) had a greater positive association with global cognition for women than men. We observed a 3-way sex*LDL*HIV interaction, with a greater negative association of the sex*LDL interaction on motor function assessed by Grooved Pegboard test (-0.59 per 10 mg/dL/ yr [-0.99, -0.19], p=0.004) and global cognition (-0.23 per 10 mg/dL/yr [-0.50, 0.04], p=0.09) in PWH than without HIV (Figure). Conclusion: BMI, LDL, and methamphetamine use had greater negative associations with cognition in women, including women with HIV, though the clinical significance of these modest differences is unclear. Future directions include evaluating interactive effects of sex and CVD risk factors on cognition in the combined cohort of PWH, accounting for HIV-related factors including ART use and viral load.

568

Poster Abstracts

567

Circulating Endothelial Microvesicles With HIV-1 Promote Cerebral Endothelial Cell Stroke Profile Auburn R Berry 1 , Samuel Ruzzene 1 , Kendra Wegerson 1 , Emily I. Ostrander 1 , Hannah L. Cardenas 1 , Hannah K. Fandl 1 , Jared J. Greiner 1 , Vinicius P. Garcia 1 , Elizabeth Connick 2 , Christopher DeSouza 1 1 University of Colorado Boulder, Boulder, CO, USA, 2 University of Arizona, Tucson, AZ, USA Background: The incidence of ischemic stroke in adults living with HIV (ALWH) is three times higher than healthy adults. Circulating endothelial cell-derived microvesicles (EMVs) have been linked to cerebrovascular events. We have previously reported that EMVs isolated from ALWH receiving antiretroviral therapy (ART) impair brain endothelial cell nitric oxide (NO) production and fibrinolytic capacity, central etiologic mechanisms in the pathogenesis of ischemic stroke. However, it is unknown whether the pathologic EMV phenotype is a consequence of HIV-1 per se or ART. The experimental aim of this study was to determine the effect of EMVs isolated from treatment naïve ALWH on brain endothelial cell nitric oxide NO production and fibrinolytic capacity. Methods: Circulating EMVs (CD 144-PE) were isolated (flow cytometry) from 16 young and middle-aged men (age range: 21-43 yr): 8 healthy (age 33±3 yr; BMI: 26.0±1.2 kg/m 2 ; BP: 113/7±22/2 mmHg) and 8 treatment naïve ALWH (10M/2F; 36±2 yr; 25.3±1.5 kg/m 2 ; BP: 117/76±3/3 mmHg; viral load: 5525 copies/mL). All men were free of overt cardiometabolic disease and not taking any medication. Human cerebral microvascular endothelial cells (hCMECs) were cultured and separately treated with EMVs from each subject. Results: Circulating EMVs were significantly higher in the treatment naïve ALWH (229±23 EMV/µL) compared with healthy adults (133±13 EMV/µL). Although total endothelial nitric oxide synthase (eNOS) expression was not significantly altered (60.1±2.3 vs 65.3±2.1 AU); active eNOS (pSer1177) (19.0±0.8 vs 26.6±1.5 AU) and, in turn, NO production (5.7±0.2 vs 6.7±0.3 µmol/L) was lower (P<0.05) in cells treated with EMVs from treatment naïve ALWH vs EMVs from healthy adults. HIV-associated EMVs also significantly reduced tissue-type plasminogen activator (t-PA) (25.5±1.2 vs 34.7±1.7 AU) and increased plasminogen activator inhibitor (PAI)-1 (146.0±4.5 vs 110.0± 3.8 AU) protein expression in hCMECs. The t-PA:PAI-1 intracellular protein ratio (5.9±0.3 vs 3.3±0.1 AU; P<0.05) was higher in HIV-1 EMV treated cells, indicative of decreased fibrinolytic capacity.

569

Verbal Learning and Memory in Well-Controlled HIV Is Similar to People Without HIV in Uganda Noeline Nakasujja 1 , Leah H. Rubin 2 , Deanna Saylor 2 , Aggrey Anok 3 , Stephen Tomusange 3 , Maria J. Wawer 4 , Jacob Bolzenius 5 , Robert Paul 5 , Gertrude Nakigozi 3 1 Makerere University College of Health Sciences, Kampala, Uganda, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 Rakai Health Sciences Program, Kalisizo, Uganda, 4 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 5 University of Missouri St Louis, St Louis, MO, USA Background: Cognitive impairment is common among people with HIV (PWH) in the United States especially in verbal learning and memory. Notably, cardiometabolic risk factors and complications and substance misuse have been associated with cognition. In Rakai, Uganda, these complications are less common in middle-aged PWH. We examined the degree to which HIV serostatus affects learning and memory in PWH and people without HIV (PWoH) in Rakai, Uganda.

CROI 2024 155