CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

10 (5-16) years. Jaccard index was 0.9. Clusters did not differ on age, sex or ethnicity. Compared to C1, PWH in C3 had significantly higher CD4/CD8 ratio and lower total and LDL cholesterol. Of the 10 KP metabolites, four anti-inflammatory metabolites of the kynurenic acid branch of the KP were significantly downregulated in C3; specifically kynurenate [C3; 0.82 (1.26 - 0.6) vs. C1; 1.22 (1.41 - 1.04), p=0.01], 8-methoxy kynurenate [C3; 0.68 (0.91 - 0.42) vs C1; 1.22 (1.98 - 0.61), p=0.03], xanthurenate [C3; 0.63 (1.09 - 0.4) vs C1; 1.19 (1.79 - 0.77), p=0.03], involved in vitamin B3 synthesis, and N-acetyl-kynurenine [C3; 0.68 (0.98 - 0.49) vs C1; 1.47 (2.4 - 0.67), p=0.004], an intermediate of NAD+ synthesis (Figure). All four downregulated KP metabolites correlated closely (all p<0.02). Conclusions: Proinflammatory profiles associated with higher prevalent CVD in PWH link to coordinated downregulation in anti-inflammatory metabolites in the KP, providing insights into the pathogenesis of CVD in PWH and supporting a role for precision medicine to identify those PWH most at risk of CVD. The figure, table, or graphic for this abstract has been removed. Risk of Obesity, Cardiometabolic Disease, and MACE After Switch to Integrase Inhibitor in REPRIEVE Emma M. Kileel 1 , Carlos Malvestutto 2 , Markella V. Zanni 3 , Carl Fichtenbaum 4 , Judith Aberg 5 , Esteban Martinez 6 , Aya Awwad 3 , Sara H. Bares 7 , Daniel Berrner 8 , Marek Smieja 9 , Matthew P. Fox 1 , Alana T. Brennan 1 , Pamela Douglas 10 , Heather Ribaudo 11 , Steven Grinspoon 3 , for the REPRIEVE study 1 Boston University, Boston, MA, USA, 2 The Ohio State University, Columbus, OH, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 University of Cincinnati Medical Center, Cincinnati, OH, USA, 5 Icahn School of Medicine at Mount Sinai, New York, NY, USA, 6 Hospital Clinic of Barcelona, Barcelona, Spain, 7 University of Nebraska Medical Center, Omaha, NE, USA, 8 University of California San Francisco, San Francisco, CA, USA, 9 McMaster University, Hamilton, Canada, 10 Duke Clinical Research Institute, Durham, NC, USA, 11 Harvard TH Chan School of Public Health, Boston, MA, USA Background: Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) has been associated with disproportionate weight gain among people with HIV (PWH), primarily in treatment-naïve populations. Few studies have explored weight and cardiometabolic outcomes beyond two years and even fewer have examined effects on major adverse cardiovascular events (MACE). Methods: Using target trial emulation, we estimated the causal effect of switching to an INSTI-based regimen, versus remaining on a non-INSTI-based regimen, on incident obesity, diabetes, hypertension, metabolic syndrome and MACE in an ART-experienced population in the REPRIEVE cardiovascular primary prevention trial. We designed a series of sequential target trials and used inverse probability of treatment weights estimated at the start of each trial to adjust for key confounders including sex, age, race, enrollment region, ASCVD risk score, statin use, ART duration and BMI. Participants not on an INSTI at REPRIEVE entry were eligible and followed until the event of interest, loss to follow-up, death (competing event) or censoring at 5 years. Hazard ratios were estimated using weighted cox-proportional cause-specific hazard models, with data pooled across all trials (N=73) and 95% confidence intervals (CI) obtained via non-parametric bootstrapping (500 samples). Results: Among 5174 participants eligible for at least one trial, 2686 (52%) switched to an INSTI-based regimen, predominantly dolutegravir (82%). Average follow-up time was similar among switchers and non-switchers (3.8 years) and average time to event following a switch to an INSTI ranged from 3.5 – 4 years depending on the outcome. Among those who switched, 7% developed obesity, 4% diabetes, 6% hypertension, 12% metabolic syndrome and 2% experienced a MACE event. Comparing those who switched to an INSTI to those who did not, we estimated an increased hazard of developing obesity (HR: 1.34, 95% CI: 1.14-1.52), diabetes (HR: 1.41, 1.13-1.70), hypertension (HR: 1.44, 1.17-1.65), and metabolic syndrome (HR: 1.18, 1.04-1.33) but not MACE (HR: 1.06, 0.67-1.53). Adjustment for NRTI choice did not meaningfully impact results. Conclusions: Leveraging a longitudinal global cohort of PWH, we found an increased risk of weight gain and cardiometabolic complications following a switch to an INSTI over 5 years of follow-up. Given the observed elevated risk profile, long-term observation of PWH switching to INSTIs will be critical to assess for future development of MACE.

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Determinants of De-Novo High-Risk Carotid Ultrasound Features in Middle-Aged People Living With HIV Napon Hiranburana 1 , Waratchaya Walailaksanaporn 2 , Aurauma Chutinet 2 , Tanakorn Apornpong 1 , Stephen Kerr 3 , Porntep Amornritvanich 4 , Anchalee Avihingsanon 5 1 HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand, 2 King Chulalongkorn Memorial Hospital, Bangkok, Thailand, 3 Chulalongkorn University, Bangkok, Thailand, 4 Police General Hospital, Bangkok, Thailand, 5 HIV-NAT, Thai Red Cross AIDS and Infectious Disease Research Centre, Bangkok, Thailand Background: People living with HIV (PLWH) are at an elevated risk for cardiovascular and cerebrovascular events, often underestimated by traditional CVD risk scores. Identifying factors driving the progression of high-risk carotid ultrasound features, indicative of subclinical atherosclerosis, is essential for improving preventive strategies and outcomes in this population. Methods: This cohort study enrolled PLWH aged ≥50 years at HIV-NAT in Bangkok. Baseline data included 10-year ASCVD risk, HIV-related parameters including duration of infection, viral load, and CD4 count, antiretroviral treatment history, metabolic profiles, inflammatory markers, and statin use. Baseline carotid ultrasound was performed between 2015 and 2018 and repeated in 2023-2024 to assess development of new high-risk features, including carotid intimal-medial thickness (CIMT) >0.9 mm, and thick (>0.4 mm) or echolucent plaques. Logistic regression was used to identify the factors associated with progression to high-risk carotid features over the study period. Results: A total of 229 participants were analyzed after excluding those with baseline CVD events or high-risk carotid features. Over a median follow-up period of 6.9 (IQR 6.6-7.4) years, 87 participants (38%) developed high-risk carotid features. Participants with progression had significantly higher baseline 10-year ASCVD risk (7.8% vs. 4.9%, p<0.001), coronary artery calcium scan (CAC) score ≥100 (18.6% vs 5%, p<0.001), diabetes (37.9% vs. 22.5%, p=0.016) and hypertension (49.4% vs. 28.9%, p=0.002). Baseline CAC score ≥100 (OR 4.5, 95% CI 1.6-12.4, p=0.016), Intermediate to high ASCVD score (OR 2.6, 95%CI 1.3-5.1, p=0.008), and protease inhibitor use (OR 2.1, 95% CI 1.2-4.0, p=0.016) were independently associated with an increased risk of developing high-risk carotid features, after adjusting for nadir CD4 count and statin use. ( Figure ) No association was found with Inflammatory markers (hsCRP, IL-6) and development of high-risk carotid features. Conclusions: Baseline intermediate to high 10-year ASCVD risk, use of protease inhibitors, and a CAC score ≥100 were associated with the progression of high-risk carotid features, suggesting PLWH with these factors are particularly vulnerable to future high-risk atherosclerosis and cerebrovascular events. Early identification and intensive targeted interventions, are essential to mitigate further cardiovascular complications in this population.

Poster Abstracts

CROI 2025 254