CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: This study found a unique NK cell population in cardiac tissue from two PLWH compared to a person without HIV. Dysregulation of the immune system, including NK cells, has been associated with cardiac fibrosis, myocarditis and cardiac transplant rejection in the HIV uninfected population. This is the first study to our knowledge to apply single cell transcriptomics to evaluate the underlying mechanisms of HIV-associated cardiovascular disease. The direct impact of HIV, immune activation and NK cells on cardiomyocytes and heart failure merits additional investigation in larger studies.

USA, 5 Dartmouth College, Hanover, NH, USA, 6 Johns Hopkins University, Baltimore, MD, USA Background: Advanced glycation end products (AGEs) are products of normal aging and are involved in the progression of different conditions such as diabetes and atherosclerosis. AGEs were recently found to be higher in people with HIV compared to uninfected controls. The effect of antiretroviral therapy (ART) on AGEs and its role in cardiometabolic complications in this population remains unknown. Methods: In ACTG A5260s, a substudy of A5257, we compared changes in serum levels of different AGEs (methylglyoxal hydroimidazolone (MG-H1), carboxymethyl and carboxyethyl lysine (CML and CEL), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal hydroimidazolone (GH-1)) in ART- naïve participants with HIV randomized to tenofovir disoproxil fumarate- emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) for 96 weeks. Linear regression models were used to study the associations between serum AGEs, and cardiometabolic outcomes of carotid intima median thickness (cIMT), visceral and subcutaneous adipose tissue (VAT and SAT), total fat, lean mass, BMI, homeostatic modal assessment – insulin resistance (HOMA-IR), leptin, and adiponectin, while adjusting for potential baseline confounders (age, sex, race, HIV-1 RNA, CD4+ T cell count, smoking, illicit drug use, alcohol use, and physical activity). Results: 214 participants were included; 90%male, 48%white, non-Hispanic, with median age of 36 yrs, HIV-1 RNA 4.58 log 10 copies/mL, and CD4 count 338 cells/μL. Most AGEs increased following 96 weeks of ART initiation, but only MG-H1 levels were significantly higher at week 96 (mean fold change of 1.15, 95% CI [1.02, 1.30]), with no differences between arms At baseline, AGEs were positively associated with HOMA-IR, even after confounder adjustment. At week 96, additional associations emerged between various AGEs and cIMT, VAT, SAT, total fat, leptin and adiponectin, even after adjusting for confounders. A two-fold increase in MG-H1 over 96 weeks was independently associated with 0.1 log 10 increase in HOMA-IR (95% CI: [0.05, 0.12]), 0.5% increase in cIMT (95% CI [0, 0.9]), and 0.7% increase in lean mass (95% CI [0.1, 1.2]). Conclusion: Initiation of ART seems to increase levels of AGEs in ART-naïve participants with HIV, regardless of regimen used. Accumulation of AGEs is independently associated with subsequent cardiometabolic risk while on ART. 637 SINGLE-CELL TRANSCRIPTOMICS OF HIV HEART TISSUE IDENTIFIES UNIQUE NK CELL POPULATION Thomas C. Martin 1 , Neil C. Chi 1 , Sara Gianella 1 , Sebastian Preissl 1 , Justin Buchanan 1 , Davey M. Smith 1 , Priscilla Hsue 2 1 University of California San Diego, La Jolla, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: Cardiovascular disease, in particular heart failure, is elevated among people living with HIV (PLWH) though the etiology of this disease process remains unclear. Using single cell RNA-seq approaches, we interrogated the spectrum of cell types and their gene expression in heart tissue from PLWH to further elucidate the underlying pathogenesis of HIV-associated heart disease. Methods: Left ventricle tissue samples were obtained from 3 participants: 1) HIV uninfected without heart failure (CTRL); 2) HIV infected without heart failure (HIV_CTRL); 3) HIV infected with non-ischemic heart failure (HIV_NICM). Both PLWH donors were virally suppressed on therapy at the time of biopsy. Samples were immediately flash frozen in liquid nitrogen at collection. Nuclei were subsequently isolated from frozen tissue and processed for single-nuclear RNA-sequencing using the 10X Chromium platform. Clustering was performed using Seurat 3.0. Results: Single nuclear transcriptomic data were obtained from 9008, 8746 and 8176 nuclei for CTRL, HIV_CTRL and HIV_NICM samples respectively. Cluster analysis was performed and clusters expressing high PTPRC (CD45+) were selected for further analysis. CD45+ cells were re-clustered and natural killer (NK) cells were identified using markers NCAM1 (CD56), Granulysin (GNLY), TBX21 and NKG7. NK cells expressed additional markers including Killer Cell Lectin Like Receptor C1 (KLRC1) and Killer Cell Lectin Like Receptor D2 (KLRD2) compared to T-lymphocytes (p-adj <10-17 and <10-7 respectively). Figure 1 shows cluster allocation for CD45+ cells from the 3 samples (panel A – CTRL, panel B – HIV_CTRL, panel C – HIV_NICM). As a proportion of all CD45+ cells, NK cells comprised 0.7%, 8.4% and 3.0% for samples CTRL, HIV_CTRL and NICM_CTRL respectively (p<0.001).

Poster Abstracts

638 CAROTID PLAQUE BURDEN IN HIV IS ASSOCIATED WITH SOLUBLE MEDIATORS AND MONOCYTES Dominic Chow 1 , Makoa Mau 1 , Howard Hodis 2 , Yanjie Li 2 , Chathura Siriwardhana 1 , Scott A. Souza 1 , Brooks I.Mitchell 1 , Scott Bowler 1 , Louie Mar A. Gangcuangco 1 , Lishomwa C. Ndhlovu 1 , Cecilia M. Shikuma 1 1 University of Hawaii at Manoa, Honolulu, HI, USA, 2 University of Southern California, Los Angeles, CA, USA Background: Maximal carotid plaque thickness (MCPT) is the measure of the largest plaque thickness in the carotid artery and reflects atherosclerotic plaque burden. MCPT may be a better predictor of cardiovascular disease (CVD) and cerebral vascular accidents (CVA) than cIMT because it identifies potential unstable arterial atherosclerotic plaques. We assessed relationships of monocyte (MO) and T-cell populations and soluble mediators in blood and MCPT. Methods: Cross-sectional and longitudinal analysis of a cohort study of CVD risk in HIV-infected participants aged > 40 years on stable antiretroviral therapy (ART) > 6 months. High resolution B-mode ultrasound images of the

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