CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: HIV-infected patients on suppressive cART who suffered an ACS (myocardial infarction or angina) without other previous nADE, were included (n=15). Peripheral blood mononuclear cells were obtained from the closest time-point (t=0), and 12 (t=-12) and 6 (t=-6) months before the ACS. HIV-infected subjects on suppressive cART without previous nADEs, matched by age, sex, CD4 T-cell counts, CD4 T-cell nadir, RNA+ for HCV and time from diagnosis (n=16) were included as control group. CCR5 expression was quantified by flow cytometry in T cells (CD4 and CD8) according to the maturation profiles: T NAIVE (CD45RA+CD27+), T CM (CD45RA-CD27+), T EF (CD45RA-CD27-) and T TD (CD45RA+CD27-). CCR7 and integrin-β7 expression was quantified in myeloid DCs (mDCs; Lin2-, HLA-DR+, CD11c+) and plasmacytoid DCs (pDCs; Lin2-, HLA-DR+, CD123+). Results: At t=0, patients with ACS showed a decrease in T CM CD8 ( p =0.03) and an increase in T TD CD8 ( p =0.04) counts compared to the control group. A progressive increase in the percentage of total CD8 T-cells expressing CCR5 was observed along the 12 months preceding the ACS. These levels were higher at t=0 ( p =0.009 for total CD8 T-cells; p =0.09 for T CM CD8; p =0.03 for T NAIVE CD8; p =0.03 for T EF CD8 and p =0.05 for T TD CD8) compared to the control group. The integrin-β7 expression in mDCs and CCR7 expression in pDCs, were strongly and positively associated with the expression of CCR5 in CD8 T-cells only in the group with ACS at t=0 ( p =0.025; Rho =0.733 and p =0.03; Rho =0.717 respectively). Conclusions: The increase in the levels of CD8 T-cells expressing CCR5 precedes the occurrence of ACS in HIV-infected patients on suppressive cART. This increase may be due to a greater recruitment of CD8 T-cells and DCs into the inflammatory focus. These new data suggest CCR5 as a newmarker of cardiovascular risk and a potential therapeutic target to prevent the development of such events.

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Soluble TWEAK May Predict Carotid Atherosclerosis in Treated HIV Infection Sahera Dirajlal-Fargo 1 ; Abdus Sattar 2 ; Manjusha Kulkarni 3 ; NicholasT. Funderburg 3 ; Grace A. McComsey 1 1 Case Western Reserve Univ, Cleveland, OH, USA; 2 Case Western Reserve Univ Sch of Med, Cleveland, OH, USA; 3 Ohio State Univ, Columbus, OH, USA

Background: Despite potent antiretroviral therapy (ART), HIV-infected subjects remain at higher risk of cardiovascular disease (CVD) when compared to the general population. Soluble Tumor Necrosis Factor Weak Inducer of Apopstosis (sTWEAK) is a cytokine that belongs to the tumor necrosis factor (TNF) family and has been proposed as a novel biomarker of cardiovascular disease risk, specifically in inflammatory conditions. This study compares levels of sTWEAK, sCD163 and the sCD163/sTWEAK ratio in HIV positive and negative patients and the cardiovascular and inflammatory factors associated with sTWEAK levels. Methods: The data for our analysis come from 174 HIV positive adults and 59 healthy controls. HIV participants were on stable antiretroviral therapy (ART), with HIV-1 RNA < 50 copies. Markers of systemic inflammation and monocyte activation, as well as carotid intima-media thickness (IMT), were assessed. Non-parametric Wilcoxon-Mann-Whitney tests were used for comparing markers by groups, and multivariable quantile regression analyses used to assess associations of sTWEAK and sCD163 with other markers of inflammation and cIMT. Results: Overall, 71%were male; 62% African Americans; median age was 39 years; median absolute CD4 was 652. HIV infected participants had reduced sTWEAK levels and increased sCD163 compared with healthy subjects (see table). In separate multivariable models, after adjusting for age, sex and race, sTWEAK and sCD163 were significantly correlated with markers of inflammation and CVD. sTWEAK was associated with IL-6 (β= 29.2, p=<0.01) and common carotid artery IMT (β= 1806.5, p=<0.01); sCD163 with IL-6 (β=6.6, p=0.01), d-dimer (β=-69.5, 0.05), VCAM (β=72.4, p=0.05), TNF RI (β=91.1, p<0.01), TNF RII (β=87.8, p<0.01), CD14+CD16+monocytes (β=7.9, p<0.01) and common carotid artery IMT (β=678.9, p=0.03); sCD163/sTWEAK ratio was also associated with common carotid artery IMT (β=-0.7, p=0.05). Conclusions: HIV-infected participants showed an inflammatory profile as shown by increased systemic inflammatory and monocyte activation markers. Soluble CD163 and sTWEAK concentrations were independently associated with carotid intima-media.

Poster Abstracts

657

Diet, Gut Integrity Markers, and Cardiovascular Disease Risk in HIV+ Adults Allison R. Webel 1 ; Abdus Sattar 2 ; NicholasT. Funderburg 3 ; Bruce Kinley 1 ; ChrisT. Longenecker 1 ; Danielle Labbato 1 ; Morgan Boucher 3 ; Grace A. McComsey 1 1 Case Western Reserve Univ, Cleveland, OH, USA; 2 Case Western Reserve Univ Sch of Med, Cleveland, OH, USA; 3 Ohio State Univ, Columbus, OH, USA Background: HIV+ adults are at increased risk of cardiovascular disease (CVD), at least partially driven by monocyte activation and inflammation. The role of dietary factors on microbial translocation, inflammation and subsequent markers of CVD has not been explored in this population. Our purpose was to describe the relationships between diet, markers of gut integrity, inflammation, and subclinical CVD. We hypothesized that higher dietary intake of fat, specifically saturated fat, would be related to worse gut integrity (intestinal fatty acid binding protein (IFAB), lipopolysaccharide binding protein (LBP)), increased inflammation (CRP, IL-6, sTNFRII), and worse markers of subclinical CVD (carotid intima-media thickness (CIMT) and coronary calcification).

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CROI 2016