CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

In multivariate regression adjusting for traditional CV risk factors and CD4 count, higher levels of plasma IL-6 (P<0.01) and CCR5 expression on monocytes (P<0.01) were associated with thicker common carotid-IMT. In addition, higher levels of plasma IL-6 (P=0.03), and higher % of CD57+ cells in CD28-CD8+ T cells (P=0.04) were correlated with thicker mean-CIMT. Levels of D-dimer, CRP, sCD14, sCD163, HLA-DR+CD38+CD8+T cells and CD16+monocytes were not associated with common carotid or mean CIMT or plaque after adjusting for traditional CV risk factors and CD4 count. Conclusions: In patients on ART with suppressed VL, higher plasma IL6 and CCR5 expression on monocytes and higher % of CD57+ cells in CD28-CD8+T cells were independently associated with thicker CIMT after adjusting for CVD risk factors and CD4 count. Dysfunction of innate immune cells and CD8 T cell senescence likely contribute to atherosclerosis in the setting of treated and suppressed HIV. 753 sCD163 Correlates With IMT and Macrophages in Aorta and Heart With HIV Infection Joshua A. Walker 1 ; Graham A. Beck 1 ; Andrew D. Miller 2 ;Tricia H. Burdo 1 ; Kenneth C.Williams 1 1 Boston College, Chestnut Hill, MA, US; 2 Cornell University, Ithaca, NY, US Background: HIV-associated mortality is decreased due to effective ART. HIV+ individuals have a two-fold greater risk of cardiovascular complications. Increased risk is likely due to chronic inflammation and virus. We have shown by FDG-PET imaging, increased monocyte/macrophage accumulation in the ascending aorta with HIV infection correlates with the numbers of non-calcified, vulnerable plaques. SIV-infected monkeys had increased inflammatory cardiac macrophages and fibrosis. We asked whether macrophage activation, accumulation, and soluble CD163 correlate with intima-media thickness (IMT) of the ascending aorta and fibrosis in left ventricular tissues with HIV infection. Methods: Matched plasma and tissue sections of left ventricle and aorta from ten HIV- and ten HIV+ individuals were obtained from the NDRI and NNTC. Levels of sCD163, a monocyte/macrophage activation marker were measured by ELISA. Matched aorta and left ventricle were scored based on the degree of inflammation, degeneration, and fibrosis. IMT of the aorta was quantified visually after an elastic stain. Levels of fibrosis in the left ventricle were assessed using a modified Massons trichrome stain. Sections were stained with antibodies recognizing CD163+, CD68+, MAC387+, and CD206+macrophages, and CD3+ T-lymphocytes. Results: Levels of sCD163 in plasma were significantly increased 62.3% in HIV+ individuals compared to controls (P<0.05, t-test). We found a 49.7% increase in the IMT of the ascending aorta in HIV+ individuals compared to uninfected. In matched left ventricular sections we found a 59.7% increase in the level of fibrosis. Levels of sCD163 significantly correlated with increased IMT as well as increased fibrosis in HIV+ individuals compared to uninfected (r=.51, r=.68, respectively p<0.05). Examination of matched tunica intima of the aortas and left ventricular sections fromHIV- and HIV+ show increased numbers of CD163+ (57.2%, 47.3%), CD68+ (59.5%, 55.0%), MAC387+ (56.3%, 53.5%) and CD206+ (32.3%, 38.9%). We found positive correlations between IMT and the numbers of macrophages present in the tunica intima, and fibrosis in the left ventricle (r=.68, r=.74, respectively p<0.05) Conclusions: These data suggest a role for monocyte/macrophage activation and accumulation in the development of cardiovascular pathology measured by IMT of the ascending aorta and fibrosis in the heart with HIV infection. 754 Non-Classical Monocytes Predict Progression of Carotid Intima-Media Thickness Dominic C. Chow 1 ; Jamie M. Kagihara 1 ; Guangxiang G. Zhang 1 ; Scott A. Souza 1 ; Brooks I. Mitchell 1 ; Beau K. Nakamoto 1 ; Kalpana J. Kallianpur 1 ; Robert J. Matyas 2 ; Lishomwa C. Ndhlovu 1 ; Cecilia M. Shikuma 1 1 University of Hawaii, Honolulu, HI, US; 2 Kaiser Permanente, Honolulu, HI, US Background: Chronic HIV-1 infection is characterized by systemic immune activation and inflammation and may contribute to cardiovascular disease (CVD) risk. We assessed relationships of monocyte [MO] subsets, CD38+HLA-DR+CD8+ T cells and various cytokines, to HIV immune dysregulation and carotid intima-media thickness (cIMT). Methods: We conducted a l ongitudinal analysis from a cohort study of CVD risk in HIV-infected subjects aged > 40 years on stable antiretroviral therapy (ART) > 6 months. Fasting blood was assessed for glucose, insulin and lipids. Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry for MO subsets [classical MO (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14 low /+CD16++)] and CD38+HLA-DR+ CD8+ T cells at baseline. Plasma biomarker multiplexing was performed. Soluble biomarkers included sE-selectin, sVCAM-1, sICAM-1, MMP-9, MPO, tPA-1, CRP, SAA, SAP, IL-1 β , IL-6, IL-8, IL-10, TNF- α , MCP-1, VEGF, IFN- γ , and NT ProBNP. High resolution B-mode ultrasound images of the right carotid bifurcation were obtained at baseline and year 2. Changes in cIMT were assessed. Pearson correlation and linear regression were used for statistical analysis. Results: We studied 50 subjects: 84%male, median age 49 (Q1,Q3: 46, 56) years, median CD4 count 461 (317,578) cells/mm 3 , with HIV RNA<50 copies/ml in 84%. Change in cIMT correlated positively with log values of non-classical MO count (r=0.37, p=0.020) and percentage (r=0.36, p=0.025), MCP-1 (r=0.42, p=0.0024) and TNF-a (r=0.30, p=0.036). Non-classical MO percentage correlated with MCP-1 (r=0.32, p=0.045). Among the monocyte subsets, only non-classical MO predicted cIMT at the bifurcation independent of age, BMI, smoking, CD4 percent and presence of HIV RNA ( β =0.13, p=0.040). Additionally, if study subjects were split by the non-classical MO percentage median value (7.33%) to High and Low levels, then the baseline cIMT value itself tended to predict the cIMT change at year 2 at the High level (R 2 =19.6%), but not at Low level of non-classical MO (R 2 =0.2%).

Poster Abstracts

Conclusions: HIV immune dysregulation is associated with elevated levels of non-classical MO. Increased non-classical MO subsets parallel increases in pro-inflammatory cytokines such as MCP-1. Non-classical MO predict progression of cIMT at the bifurcation in HIV-infected individuals on suppressive ART independent of traditional cardiometabolic and HIV immunovirologic factors, and may contribute to CVD.

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CROI 2015