CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Of 1,555 individuals included in the lipid analyses, 590 initiated INSTI without TAF, 285 INSTI+TAF, 382 protease inhibitor (PI), and 298 non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens. Most (86%) were men who have sex with men, 76% originating from Europe/N. America with median (IQR) age at SC 36 (28-44) years. Median (IQR) baseline TCHOL and TG were 161 (139, 186) and 109 (80, 156) mg/dL, respectively. In multivariable models, INSTI+TAF was associated with the fastest TCHOL increase after month 6 of treatment (p<0.001), and faster TG increase only during the first 6 months (p=0.038) compared to NNRTIs. INSTIs without TAF were only associated with a relatively slow increase in TCHOL after month 6 (p=0.027) compared to NNRTIs. In 1189 individuals with no baseline hyperlipidaemia, only PIs were significantly associated with increased hazard of developing hyperlipidaemia (aHR=1.75 vs. NNRTIs; 95% CI:1.26-2.43; p=0.001). Risk of developing hypertension in 1417 hypertension-free at baseline individuals was elevated in those on INSTI+TAF but not INSTI without TAF (aHR=1.51; 95%CI:1.07-2.13; p=0.019 and aHR=1.14; 95%CI:0.85-1.53; p=0.392, respectively). Conclusions: Lipid levels and BP appear to rapidly increase even at this early stage of infection. Our findings stress the importance of informed ART regimen decisions, acknowledging the potential for different effects on cardiometabolic parameters. Potential of the Short Chain Fatty Acid Caproic Acid in Protection Against CVD in HIV Infection Florent Bertrand 1 , Minh Tran 1 , Rémi Bunet 1 , Hardik Ramani 1 , Sylla Mohamed 1 , Madeleine Durand 1 , Carl Chartrand-Lefebvre 2 , Petronela Ancuta 2 , Nicolas Chomont 2 , Alan Landay 3 , Mohamed El-Far 1 , Cécile Tremblay 2 1 Centre de Recherche du CHUM, Montreal, Canada, 2 Université de Montréal, Montreal, Canada, 3 University of Texas Medical Branch, Galveston, TX, USA Background: We have recently shown that the proinflammatory cytokine IL-32 is associated with arterial stiffness and cardiovascular disease in people with HIV (PWH). We also demonstrated that IL-32 induces coronary artery endothelial cell (CAEC) inflammation and dysfunction and that IL-32 alterations in PWH with subclinical atherosclerosis are associated with a deficit in the short-chain fatty acid (SCFA) caproic acid. In this study, we investigated the beneficial effect of the intestinal microbiota-driven SCFAs acetic, butyric, propionic, valeric and caproic to alleviate the IL-32-mediated CAEC dysfunction. Methods: Human primary CAEC from Creative Bioarray are isolated from human coronary artery and used between passage 3 to passage 12. CAEC were conditioned with the different SCFAs at similar concentrations (1mM) before being stimulated with IL-32γ (the longest and most inflammatory IL-32 isoform) at 500ng/ml. The impact of SCFAs on upregulation of the CAEC typical dysfunction markers IL-6, CCL-2, ICAM-I and VCAM-I was measured in cell supernatants by ELISA. Differences in the potential of SCFAs to protect against the upregulation of the dysfunction markers were calculated with one-way ANOVA test. Cell viability of SCFA-treated cells was carried by measuring the cell release of the Lactate dehydrogenase LDH enzyme by ELISA. Results: Caproic acid was the only SCFA that diminished the impact of IL-32γ on coronary artery endothelial cells dysfunction by simultaneously downregulating the expressions of IL-6, CCL-2, ICAM-I and VCAM-I (2.4±0.6, 1.2±0.1, 2±0.5, and 2.5±0.9 fold, p=0.0003, p=0.02, p=0.03, and p<0.0001, respectively) without impacting cell viability. In contrast, acetic acid inhibited CCL-2 (p=0.02) and VCAM-I (p=0.015) while propionic, butyric, and valeric acids only inhibited V-CAM-I (p=0.0003, p<0.0001 and p<0.0001, respectively) but not IL-6, CCL-2 or ICAM-I. These results suggest that caproic acid has a dominant positive effect in restoring endothelial cell functions, which are dysregulated by the inflammatory cytokine IL-32. Conclusions: Our results uncover the potential benefits of caproic acid (a short chain fatty acid that we recently shown to be diminished in stool samples collected from PWH with subclinical atherosclerosis) in reversion of the endothelial cell dysfunction mediated by the inflammatory cytokine IL-32. These results warrant further investigations to the therapeutic potential of caproic acid in PWH with risk of cardiovascular disease. The figure, table, or graphic for this abstract has been removed.

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Genomic Analyses of Cardiovascular Risk in People With HIV From the MVP Cohort Boghuma K. Titanji 1 , Amonae Dabbs-Brown 1 , Jennie T. Mather 2 , Qin Hui 1 , Suyu Zhang 1 , Catherine Mezzacappa 3 , Roxane Rohani 4 , Matthew S. Freiberg 5 , Evelyn Hsieh 3 , Brian Agan 6 , Julie A. Womack 3 , Ke Xu 3 , Rafick P. Sekaly 1 , Yan V. Sun 1 , Vincent C. Marconi 1 1 Emory University, Atlanta, GA, USA, 2 Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA, 3 Yale University, New Haven, CT, USA, 4 Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA, 5 Vanderbilt University Medical Center, Nashville, TN, USA, 6 Uniformed Services University of the Health Sciences, Bethesda, MD, USA Background: Cardiovascular disease (CVD) is the third leading cause of death among people with HIV (PWH) globally. Despite effective antiretroviral therapy, PWH have twice the CVD risk of the general population. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) studies have been conducted in the general population to demonstrate the important genetic contribution to CVD risk, but genomic studies of CVD in PWH remain limited. Methods: We performed a GWAS in adult PWH from the Million Veteran Program (MVP) to identify any genetic loci associated with CVD outcomes among PWH of African (AFR), European (EUR), and Hispanic (HIS) ancestry. We also assessed the performance of an established PRS of coronary artery disease (CAD) for predicting CVD outcomes in MVP PWH. HIV infection was defined using validated ICD codes for the MVP cohort, detectable viral load, or antiretroviral use for >30 days. Incident CVD outcomes included myocardial infarction (MI), ischemic stroke (IS), peripheral arterial disease (PAD), cardiovascular death, and a composite CVD outcome (any of the above). After standard quality control, TOPMed-imputed SNPs were used for ancestry-specific GWAS of common variants (minor allele frequency >5%), followed by a multi-ancestry meta analysis adjusting for sex and age. Statistical significance was defined at the conventional GWAS threshold of p < 5 ×10 - ⁸ with Bonferonni correction and alpha = 0.05 Results: The cohort included 7,951 PWH (94.2% male, 43.9% AFR, 10.5% HIS) with a mean age of 51.7 years. Incident outcomes included 330 (4.15%) MI, 337 (4.24%) IS, 845 (10.63%) PAD, and 79 (0.99%) CVD deaths. Multi-ancestry GWAS identified a significant association between the composite CVD outcome in PWH and a locus on chromosome 2 near the NAT8 gene (rs4852953; β=0.3; p=4.26×10 - ⁸). The CAD PRS was predictive of MI and composite CVD outcome in AFR (MI: p=1.89×10 - ²; composite: p=4.12×10 - ²) and EUR (MI: p=1.48×10 ‑ ⁴; composite: p=4.26×10 - ²) but less robust in HIS PWH (MI: p=2.73×10-2; composite: p=6.51×10 - ¹). Conclusions: In a multi-ancestry cohort of PWH, a CAD PRS validated in Europeans predicted MI and composite CVD outcomes. Polymorphisms in the NAT8 have potential associations with CVD through their influence on oxidative stress, blood pressure and kidney function. NAT encodes for N acetyl transferase 8 an enzyme that is crucial in regulatory pathways of cellular oxidative stress. Loci identified in GWAS of PWH, warrant replication in larger studies with refined phenotyping

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Poster Abstracts

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The Additive Value of Coronary Calcium in Identifying Cardiovascular Risk in Ageing People With HIV Maithili Varadarajan 1 , Ruth Byrne 2 , Abtehale Al-Hussaini 2 , Brian Halliday 3 , Edward Nicol 3 , Alan Winston 4 , Marta Boffito 2 1 Chelsea and Westminster Hospital, London, UK, 2 Chelsea and Westminster NHS Foundation Trust, London, UK, 3 Royal Brompton and Harefield Hospitals, 4 Imperial College London, London, UK Background: In people without HIV, high Coronary Artery Calcium Scores (CACS) correlate with an increased risk of major cardiovascular and cerebrovascular events (MACE). HIV is independently associated with raised

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