CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

653

Association of T Cell and Macrophage ActivationWith Vascular Health in HIV Heather Grome ; Louise Barnett; Cindy Hager;Timothy R. Sterling; Spyros A. Kalams; John R. Koethe Vanderbilt Univ Sch of Med, Nashville, TN, USA

Background: Delineating the relationships between vascular health, inflammation, and immune activation is important to the study of cardiovascular disease (CVD) risk in HIV- infected persons on long-term antiretroviral therapy (ART). We assessed associations between T cell and macrophage activation, brachial artery flowmediated dilation (FMD; a functional measure of arterial smooth muscle response to ischemia), and circulating intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1; two markers of endothelial cell activation). Methods: We enrolled 70 HIV-infected adults on efavirenz, tenofovir, and emtricitabine with sustained virologic suppression for >2 years, a CD4+ count >350 cells/µl, no known diabetes or CVD, and no statin use, and measured FMD, ICAM-1, and VCAM-1. Activated (CD38+), senescent (CD57+PD1+), and memory (CD45RO+) CD4+ and CD8+ T cells were measured by flow cytometry. Soluble markers of macrophage activation (sCD14, sCD163, and macrophage inflammatory protein-1α [MIP-1α]) were measured by ELISA and cytometric bead array. The relationships between immunologic and vascular parameters were assessed using regression models adjusted for age, sex, smoking, duration of ART, and body mass index. Results: Median age was 45 years (IQR 39, 50), median CD4+ count 701 cells/µl (IQR 540, 954), 43%were female and 54% non-white. Lower brachial artery FMD was associated with high CD8+ T cell activation (p<0.01), but FMD was not associated with other T cell subsets or macrophage markers. In contrast, higher ICAM-1 was associated with higher sCD14, sCD163, and MIP-1α (p<0.01 for all), and higher VCAM-1 with sCD163 and MIP-1α (p<0.01 for both). Furthermore, low CD4+ activation and high CD4+memory cells were associated with high VCAM-1 (p=0.01 for both). Results were similar when adjusted for race, hepatitis C, and CD4 count. Conclusions: In HIV-infected adults with virologic suppression, cytotoxic CD8+ activation was associated with impaired brachial artery smooth muscle relaxation. In contrast, increased soluble inflammatory markers, possibly shed by vascular macrophages, were associated with endothelial cell activation. This suggests T cell and macrophage activation adversely affect vascular health via differing mechanisms, and CVD studies in HIV patients should utilize both functional and biomarker vascular assessments. A possible link between a robust CD4+memory cell expansion on ART and endothelial activation should be investigated further. 654 Background: The underlying mechanism for endothelial dysfunction and HIV-associated cardiovascular disease (CVD) remains unknown. Immune activation and chronic inflammation persist even in the setting of effectively treated HIV. T cell activation leads to T cell dysregulation and may be one underlying cause of chronic inflammation in HIV- infected individuals. The purpose of this study was to determine whether T cell activation and inflammatory markers in HIV-infected individuals are associated with endothelial dysfunction, a predictor of future cardiovascular events. Methods: We performed a cross-sectional study of immune activation and inflammatory markers with endothelial function in 359 HIV-infected adults. Endothelial function was assessed using flow-mediated vasodilation of the brachial artery (FMD) and reactive hyperemia (RH). T-cell activation including HIV and CMV-specific responses were assessed using flow cytometry in peripheral mononuclear blood cells. Results: The mean age was 49 ± 10 years and 84%were male, 76%were on ART, 31% smokers, and 18%with hepatitis C. The median FMD was 4.0% (IQR 2.6, 5.5) and the median RH was 57% (IQR 45, 79). After multivariable adjustment for demographics, traditional CV and HIV risk factors, CMV IgG was the only inflammatory marker associated with impaired FMD (-11.7% per doubling, p = 0.002). In comparison, higher TNF-α (-44.5% per doubling, p = 0.007) and higher neopterin (13.9% per doubling, p = 0.035) were associated with lower (worsened) RH. Other inflammatory markers including hsCRP, IL-6, sCD163, and D-dimer were not associated with FMD or RH. Only CD4+IFN+ (CMV specific) T cell activation was associated with lower RH (-4.5% per doubling, p = 0.028) and none of the other assessments of T cell activation were predictive of either FMD or RH. When the analysis was restricted to treated and suppressed individuals only, the results remained the same. Conclusions: Certain inflammatory markers such as CMV IgG, TNF-α, and neopterin (a marker of plaque instability) were independently predictive of endothelial dysfunction in HIV-infected individuals. CMV-specific T cell activation was independently associated with worsened RH. Unlike FMD, RH measures microvascular function and thus could explain the different findings between the two outcomes. Interventions targeted at reducing inflammation particularly in the setting of CMV infection may improve endothelial function and decrease HIV-associated CVD. Effect of T-Cell Activation and Inflammation on Endothelial Dysfunction in HIV Arjun Sinha ;Yifei Ma; Rebecca Scherzer; Danny Li; Steven G. Deeks; Peter Ganz; Priscilla Hsue Univ of California San Francisco, San Francisco, CA, USA

Poster Abstracts

655 CCR5+CD8+ T-Cell Levels Are AssociatedWith Cardiovascular Events in Patients on cART Laura Tarancón 1 ; Rebeca S. de Pablo 2 ; Isaac Rosado 3 ; Beatriz Dominguez 3 ; Miguel Genebat 4 ; María José Polaino 5 ; Mohammed Rafii-El-Idrissi Benhnia 4 ;Yolanda M. Pacheco 3 ; Manuel Leal 4 ; Ezequiel Ruiz-Mateos 4 1 BioMed Inst of Sevilla, Sevilla, Spain; 2 BioMed Inst of Seville, Sevilla, Spain; 3 Inst of BioMed of Seville (IBiS), Seville, Spain; 4 BioMed Inst of Seville, Seville, Spain; 5 BioMed Inst of Seville, Sevilla, Spain Background: Acute coronary syndrome (ACS) is one of the most frequent non-AIDS-defining Event (nADEs). Previous cross-sectional studies have observed an increased incidence of atherosclerosis and higher T lymphocyte activation in HIV patients compared to healthy subjects. However, there are no longitudinal studies analyzing the characteristics of T and dendritic cells (DCs) phenotypes that precede an ischemic event in these patients. The aim of this work was to study in peripheral blood the T and DCs phenotype of HIV patients with ACS on suppressive cART along the year before the nADE.

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CROI 2016