CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

assay. We measured carotid intima-media thickness (IMT) longitudinally with ultrasound and aortic inflammation and hematopoietic metabolic activity using cross-sectional 18F-FDG-PET. Inflammatory biomarkers were measured with a multiplex electrochemiluminescence assay. We used linear regression with adjustment for age, sex, nadir CD4 count, smoking, hypertension, diabetes, and hyperlipidemia to adjust for potential confounders. Results: We included 231 PWH (52±9 years, 7% female). 32 (14%) had CHIP with median variant allele fraction of 3.1%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Only age was associated with CHIP (OR 2.3 per decade older, 95%CI 1.2-3.9; p=0.003. Among N=165 (CHIP=22), baseline mean IMT was 1.0 mm with and without CHIP (p=0.63), unchanged after adjustment (Figure). CHIP was not associated with prevalent (p=0.82) or incident plaque (p=0.48). Over 3.2 years, IMT progression was faster among those with CHIP (0.033 mm/year; p=0.10), attenuated after adjustment (0.022 mm/year; p=0.27). Among 80 with FDG-PET, CHIP (n=12) was associated with higher lymph node metabolic activity (p=0.03) that was attenuated in reference to background activity (p=0.69) and adjusted for risk factors (p=0.22), with a similar trend for spleen activity (p=0.14). CHIP was not strongly associated with arterial inflammation (p=0.83), bone marrow activity (p=0.50), inflammatory markers, or viral persistence markers. Conclusion: Among PWH, CHIP mutations were not associated with subclinical atherosclerosis or arterial inflammation, proposed mechanisms of how CHIP could cause CVD. Associations with lymph node and spleen activity suggests CHIP may be induced by HIV reservoirs or induce increased reservoir activity. Clinical outcomes studies are needed to ascertain the impact of CHIP on CVD in HIV.

and plasma HIV RNA <50 copies/ml. Cases were PWH on ART with incident vascular event (VE): coronary artery disease (CAD), CAD with myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolus (PE), cerebrovascular accident (CVA, stroke), and/or peripheral arterial disease (PAD). Cases were age- and gender-matched 1:4 to controls. Cryopreserved plasma (>1 year prior to censor date) were used to quantify IL-1β signaling cytokines (IL-1β, IL-6, and IL-18) using a high-sensitivity assay (MesoScale). Logistic regression models adjusted for potential vascular covariates (hypertension, hyperlipidemia, diabetes mellitus, tobacco use, alcohol use, family history of vascular disease) were fit to estimate odds ratios (ORs). Results: A total of 200 cases and 802 controls were included. Participants were mostly male (92%), White (43%; 41% Black, 10% Hispanic), with a median age=31 years, nadir CD4+ T cell count=290 cells/mm 3 , pre-ART viral load=log 10 4.6 copies/mL, ART suppression=6.8 years, and HIV seroconversion to ART initiation=1.8 years; overall characteristics were similar between cases vs. controls. Plasma IL-1β, but not IL-18 or IL-6, significantly predicted the composite outcome of any vascular event (OR_VE=1.21, 95% CI:1.10, 1.33) and predicted CAD, MI, and PE. The associations with PE and CAD remained significant in multivariate models adjusted for hypertension and hyperlipidemia (OR_PE=1.38, 95% CI: 1.09, 1.73 and OR_CAD=1.21, 95% CI: 1.07, 1.38). Conclusion: Recent high sensitivity assays can now discriminate within- and across-individual plasma IL-1β levels. To our knowledge, this is the largest epidemiologic study of plasma IL-1β in PWH, as well as in the general population, in relation to vascular events. Our findings suggest that IL-1β may be a critical upstream regulator of IL-6 and have important implications for therapeutic strategies to reduce inflammation and vascular comorbidities in PWH on ART.

Poster Abstracts

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Activated and Exhausted CD8+ T-Cell Subsets Associate With Carotid Atherosclerotic Plaques in PLHIV Marc Blaauw 1 , Adriana Navas 1 , Nadira Vadaq 1 , Vasiliki Matzaraki 1 , Elise M. Meeder 1 , Wilhelm A. Vos 1 , Albert L. Groenendijk 2 , Louise E. van Eekeren 1 , Gert Weijers 1 , Marvin Berrevoets 3 , Hans Koenen 1 , Marien I. de Jonge 1 , Andre J. van der Ven 1 , Joost Rutten 1 , Niels P. Riksen 1 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Erasmus University Medical Center, Rotterdam, Netherlands, 3 Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands Background: Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of morbidity and mortality in people living with HIV (PLHIV). Understanding the association between circulating immune cells and carotid plaque presence in PLHIV holds the potential to identify novel immunological mechanisms driving plaque progression in PLHIV. Flow cytometry, allows identification and quantification of immune cells within heterogeneous populations. Methods: Our study analyzed data from the 2000HIV study (NCT03994835), comprising 1188 individuals with valid carotid ultrasound, without previous ASCVD and with valid high-dimensional flow cytometry measurements. This Dutch multi-center cross-sectional study focuses on virally suppressed PLHIV and is divided into a discovery cohort (n= 989) and validation cohort (n= 194). High dimensional flow cytometry was performed to identify the major blood immune cell subsets (403 populations) and their functional status. We performed linear regression models adjusted for age, sex and seasonality. Findings from the discovery cohort after correction for multiple testing were validated in the validation cohort. Results: In total 584 participants (49.2%) had a carotid plaque. Our findings revealed higher numbers of different CD8+ T cell subsets in individuals with

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Clonal Hematopoiesis in HIV and Atherosclerosis, Arterial Inflammation, and Hematopoietic Activity Matthew S Durstenfeld 1 , Katherine J. Kentoffio 2 , Alexandra J. Teng 3 , Shady Abohashem 4 , Danny Li 1 , Rebecca Hoh 1 , Steven G. Deeks 1 , Alexander G. Bick 5 , Ahmed A. Tawakol 4 , Priscilla Y. Hsue 1 1 University of California San Francisco, San Francisco, CA, USA, 2 Beth Israel Deaconess Medical Center, Boston, MA, USA, 3 Kaiser Permanente, Oakland, CA, USA, 4 Massachusetts General Hospital, Boston, MA, USA, 5 Vanderbilt University, Nashville, TN, USA Background: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) and common in HIV, but whether CHIP contributes to atherosclerosis in HIV is unknown. We hypothesized that CHIP is associated with atherosclerosis, arterial inflammation, and hematopoietic activity among people with HIV (PWH). Methods: In this observational study, we studied treated, suppressed PWH ages 35-70 years old with ≥1 CVD risk factor. CHIP mutations were detected from peripheral blood mononuceleic cells with a validated targeted sequencing

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