CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

TUESDAY, FEBRUARY 24, 2015 Session P-P7 Poster Session

Poster Hall

2:30 pm– 4:00 pm Endothelial Functions and Cerebral Vasoreactivity 757 Role of Angiopoietin 1, Angiopoietin 2, and Endothelial Function in HIV Mark L. Dela Cruz 1 ;Yifei Ma 1 ; Rebecca Scherzer 1 ; AlanWu 2 ; Kristinalisa Maka 1 ; Steven Deeks 1 ; Peter Ganz 1 ; Priscilla Hsue 1 1 University of California San Francisco, San Francisco, CA, US; 2 Blood Systems Research Institute/University of California San Francisco, San Francisco, CA, US

Background: HIV-infected patients have increased risk for cardiovascular disease (CVD). The underlying mechanism likely involves impaired endothelial function, a precursor of atherosclerosis. Endothelial homeostasis is promoted by the Tie2 receptor system through its agonist, angiopoietin-1 (Ang1) while its antagonist, the inflammatory protein angiopoietin-2 (Ang2), promotes endothelial activation. We hypothesized that HIV infection is associated with decreased Ang1 and increased Ang2 levels, leading to impaired endothelial function. Methods: We performed a cross-sectional analysis of Ang1 and Ang2 serum levels by ELISA, among 89 HIV-infected individuals, and 46 uninfected controls. Endothelial function was measured by flow-mediated dilation of the brachial artery (FMD). Generalized linear regression models and Spearman correlations were used to determine the association of HIV to Ang1/Ang2 levels and FMD. Results: The median age was 49 yrs and 87%were male. Compared to controls, HIV-infected individuals were younger (median age 45 yrs vs 53 yrs, p=0.03), less likely to be male (82% vs 98%, p=0.03), and more likely to have renal disease (eGFR<60) (13.5% vs 2.2%, p=0.04). Forty-seven (53%) of the HIV-infected individuals were effectively treated and suppressed with antiretroviral therapy (ART). Compared to controls, Ang1 levels were lower in HIV-infected individuals (median 2219 pg/ml, IQR 1022 to 4280, p= 0.01) while Ang2 levels were higher (median 2147 pg/ml, IQR 1617 to 3106, p=0.06). After adjustment for traditional risk factors, Ang1 levels remained significantly lower in HIV subjects compared to controls (-43.8%, p=0.018) while Ang2 levels were no longer different (p=0.65). Individuals on effective ART had 29% lower Ang1 levels compared to controls in adjusted analysis (p=0.01) and lower Ang1 levels were independently associated with impaired FMD (p<0.001). Conclusions: Circulating Ang1 levels are reduced among HIV-infected individuals compared to controls, even in subjects on effective ART. Lower Ang1 is independently associated with impaired endothelial function. These data suggest that HIV infection leads to an imbalance between Ang1 and Ang2, resulting in endothelial dysfunction through the Tie2 receptor system. Our findings reveal a potential new target for mitigating CVD risk in the setting of treated HIV infection. 758 HIV-Infected Persons With Type 2 Diabetes Have Evidence of Endothelial Dysfunction Malene Hove 1 ; Julie C. Gaardbo 3 ; Hedda Hoel 3 ; Lillian Kolte 2 ; AllanVaag 1 ; Jan Gerstoft 1 ; Henrik Ullum 1 ; MariusTroseid 3 ; Susanne D. Poulsen 1 1 Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; 2 Hvidovre Hospital, University Hospital of Copenhagen, Hvidovre, Denmark; 3 Oslo University Hospital, Ullevål, Norway Background: Increased incidence of cardiovascular diseases (CVD) in HIV-infected persons compared to the general population has been described. Likewise, Type 2 diabetes (T2D) is an independent risk factor for CVD. T2D is characterized by endothelial dysfunction. Endothelial dysfunction has been suggested as possible cause to increased risk of CVD in HIV infection. Little is known about the combined effect of HIV infection and T2D on endothelial function. We hypothesized an additive effect of HIV infection and T2D on endothelial dysfunction. Methods: A cross-sectional study was performed including 50 HIV-infected persons on cART and with HIV RNA < 200 copies/mL (n=25 with T2D (HIV+T2D+), n=25 without T2D (HIV+T2D-)), and 50 HIV-negative persons (n=22 with T2D (HIV-T2D+) and n=28 without T2D (HIV-T2D-). Groups were matched on age and sex, and groups of HIV-infected patients were matched on CD4 cell count (672 cells/mL vs 663 cells/mL). Assymetric dimethylarginine (ADMA) and Trimethylamine-N-oxid (TMAO) were used as markers of endothelial dysfunction and analyzed in snap-frozen EDTA-plasma using high performance liquid chromatography and Stable isotope dilution, respectively. Differences between groups were analyzed using one-way ANOVA and t test. Data are given as mean (95%CI). Results: HIV+T2D+ had elevated ADMA (0.67 μ M (0.63-0.72) compared to HIV+T2D- (0.60 μ M (0.57 - 0.64) p=0.017), HIV-T2D+ (0.57 μ M (0.51-63) p=0.008) and HIV-T2D- (0.55 μ M (0.52- 0.58) p<0.001) (FIG 1). In contrast, no differences in TMAO level between the four groups were found( HIV+T2D+: 7.51 μ M (4.28-10.75), HIV+T2D-: 5.58 μ M (3.55-7.61), HIV-T2D+: 4.56 μ M (3.89- 5.22) and HIV-T2D- 7.07 μ M (3.63-10.52)). However, we found a positive correlation between ADMA and TMAO in HIV+T2D+ and HIV+T2D- (p=<0.001, r=0.524).

Poster Abstracts

FIG 1 Conclusions: Evidence of endothelial dysfunction was found in HIV-infected persons with T2D compared to HIV-infected persons without T2D. Thus, Our data indicate an addictive effect of HIV infection and T2D on endothelial dysfunction possibly leading to elevated risk of CVD. This underlines the clinical importance of effective CVD prevention strategies in this group of patients.

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CROI 2015