CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

right carotid artery were obtained to assess maximal carotid plaque thickness at baseline and year 2. Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry for MO subsets [classical MO (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14low/+CD16++)] and T-cell (CD38+HLA-DR+) activation at baseline. Soluble biomarkers sE-selectin, sVCAM-1, sICAM-1, MMP-9, MPO, PAI-1, CRP, SAA, SAP, IL-1β, IL-6, IL-8, IL-10, TNF-α, MCP-1, VEGF, IFN-γ, NT ProBNP and Apolipoproteins were measured by Luminex technology. Variables were transformed using Log 10 -transformation. Spearman correlation and multivariable regression were used for statistical analysis to identify factors associated with MCPT. Results: We studied 125 HIV+: 85%male, 58% Caucasian, with a median age of 51, median CD4 count was 477 cells/μL (Q1: 325, Q3: 612), 86% undetectable HIV viral load. MCPT correlated with non-classical monocyte (r=.451, p=.046), MCP-1 (r=.487, p=.016), TNFα (r=.474 p=.019), sVCAM1 (r=.472, p=.020), ApoB6 (r=-.473, p=.019) and IL-6 (r=.455, p=.025). In a multivariable regression model, MCP-1, TNFα, and sVCAM1 remained significant even after adjustment for age. Longitudinal analysis of 15 HIV+ participants with two MCPT assessments revealed no correlation with types of ART; lipid lowering, hypertensive and antiplatelet medications; or illicit drug use. Conclusion: Worsening carotid plaque burden is associated with increased non-classical monocytes and inflammatory markers. Changes in MCPT were not associated with anti-lipid therapy. 639 INCREASED LEUKOCYTE/PLATELET INTERPLAY WITH ENDOTHELIUM IN ABC-TREATED HIV PATIENTS Maria Amparo Blanch-Ruiz 1 , Ainhoa Sanchez-Lopez 1 , Raquel Ortega-Luna 1 , Patricia García-Martínez 1 , Samuel Orden 1 , Maria Angeles Martinez-Cuesta 1 , Ramon Ferrando-Vilata 2 , Maria J. Galindo 2 , Angeles Alvarez 1 , Juan V. Esplugues 1 1 University of Valencia, Valencia, Spain, 2 Hospital Clinic of Valencia, Valencia, Spain Background: Abacavir (ABC) has been associated with a risk of myocardial infarction. We have demonstrated experimentally that clinical concentrations of ABC added in vitro, but not of tenofovir disopropil fumarate (TDF), have pro-inflammatory (it induces leukocyte-endothelium interactions) and pro-thrombotic (it causes the interplay of platelets with endothelial cells or leukocytes) actions. Furthermore, ABC promoted thrombus formation in a well-established in vivo model. The aim of the present study was to test the pro-inflammatory and pro-thrombotic status of HIV patients undergoing ABC versus TDF treatment by analysing leukocyte- and/or platelet-endothelium interactions in cells isolated from blood of these two groups of HIV patients. Methods: This is a non-aleatorized prospective observational study in which we used blood cells from HIV-patients at Hospital Clínico Universitario de Valencia who had been receiving treatment, for at least 6 months, with a ART regime that included either ABC or TDF. Interactions of isolated leukocytes (peripheral blood mononuclear cells, PBMC) – rolling and adhesion - and isolated platelets – adhesion - with a non-infected endotheliummonolayer were evaluated by means of a parallel-plate flow chamber system. Platelets were labelled with an anti-CD41 (specific platelet marker) antibody linked to Alexa-Fluor®488 in order to visualize them by Epi-fluorescence microscopy. Results: 39 patients were included in the study, 18 of whomwere receiving ABC and 21 of whomwere receiving TDF. There were no significant differences in demographic and cardiovascular risk parameters between the two groups. PBMC rolling (Figure 1A) and adhesion (Figure 1B) along the endotheliumwere significantly higher in the ABC group than in the TDF group. Moreover, the number of platelets adhering to endothelial cells was higher in the ABC versus TDF group (Figure 1C). Conclusion: Treatment with ABC enhances PBMC-endothelium interactions, thus promoting the initial phases of the inflammatory process. Furthermore, it induces platelet adhesion to endothelial cells, which is an important step in thrombus formation. Our results give support to the increased risk of myocardial infarction observed in ABC-treated HIV patients.

640 FIBROBLAST GROWTH FACTOR 21: EFFECT OF HIV THERAPY AND ASSOCIATION WITH CVD RISK Corrilynn O. Hileman 1 , Sarah E. Scott 2 , Beth A. Zavoda-Smith 2 , Grace A. McComsey 2 1 MetroHealth Medical Center, Cleveland, OH, USA, 2 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: Fibroblast growth factor 21 (FGF21) is a pleiotropic signal molecule for several metabolically active organs. The liver releases FGF21 in response to a broad range of stress conditions resulting in beneficial effects on glucose, lipid and energy homeostasis. FGF21 may be part of a compensatory response to offset atherosclerosis in certain disease states. People with HIV (PWH) are at heightened risk for cardiovascular disease (CVD). Whether FGF21 is modified by antiretroviral therapy (ART) or could serve as a marker for subclinical atherosclerosis in PWH is not known. Methods: Fasting plasma FGF21 concentrations were quantified by ELISA from ART-naïve HIV+ adults enrolled in a longitudinal study of carotid intima media thickness (IMT) progression and in ART-treated HIV+ adults matched by sex, race and body mass index (BMI) at entry (all participants), and weeks 48 and 96 (those who initiated ART at entry). Multivariable linear regression and mixed effects linear modeling were used to explore associations between ART status, FGF21 and common carotid artery (CCA) IMT at entry and over time. Results: 162 participants (81 ART-naïve; 81 ART-treated) were included. Groups were similar except ART-treated were older (median 48 vs 41; p<0.01) had higher waist-to-hip ratio (0.96 vs 0.92; p=0.03) and HOMA-IR (2.4 vs 1.4) and lower nadir CD4+ count (191 vs 388 cells/mm 3 ). Overall, 80%were men; 63%were black; 52%were current smokers. Of those on ART, 60%were on an NNRTI, 36% on a PI, and all had HIV-1 RNA <20 copies/ml. FGF21 was higher in ART-treated (218 vs 166 pg/ml; p=0.01), but adjusting for age, waist-to-hip ratio, glucose or nadir CD4+ count attenuated the association. Older age, white race, current smoking, higher glucose, waist-to-hip ratio and interleukin-6 (IL6) were independently associated with higher entry FGF21. In those who initiated ART (n=51), regardless of ART class, FGF21 levels did not change significantly over 96 weeks (p=0.55). Unadjusted, entry FGF21 was positively associated with entry CCA IMT (p=0.02); however, adjusting for age, waist-to-hip ratio, or inflammation (IL-6 or soluble tumor necrosis factor alpha receptor-1) attenuated the association. Entry FGF21 tended to predict CCA IMT progression (p=0.08), but again the association was attenuated with adjustment for age or waist-to-hip ratio. Conclusion: FGF21 concentrations are not decreased after successful ART, and although closely associated with traditional CVD risk factors, FGF21 did not independently predict IMT progression on ART. 641 MONOCYTE ACTIVATION AND CARDIAC-MRI–DERIVED VASCULAR DYSFUNCTION AMONG WOMEN WITH HIV Mabel Toribio 1 , Magid Awadalla 1 , Evelynne S. Fulda 1 , Adam Rokicki 1 , Takara L. Stanley 1 , Lidia Szczepaniak 2 , Michael D. Nelson 3 , Michael Jerosch-Herold 4 , Tricia H. Burdo 5 , Tomas G. Neilan 1 , Markella V. Zanni 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 MRS Consulting, Albuquerque, NM, USA, 3 University of Texas, Arlington, TX, USA, 4 Brigham and Women's Hospital, Boston, MA, USA, 5 Temple University, Philadelphia, PA, USA Background: Women with HIV (WHIV) on ART face an increased risk of cardiovascular disease (CVD), including heart failure. Aortic vascular dysfunction, reflected by increased aortic pulse wave velocity (aPWV), presages, predicts, and promotes adverse CVD outcomes. Moreover, aortic vascular dysfunction – a proxy for vascular aging – is highly influenced by the local inflammatory milieu. Comparisons of aortic vascular function among predominantly male cohorts with vs. without HIV have yielded conflicting

Poster Abstracts

CROI 2020 232