CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

755 TMAO and HIV-Associated Atherosclerosis Arjun Sinha 1 ;Yifei Ma 1 ; Rebecca Scherzer 2 ; Courtney Carroll 1 ; Steven Deeks 3 ; Peter Ganz 1 ; Priscilla Hsue 1 1 San Francisco General Hospital, San Francisco, CA, US; 2 San Francisco VA Medical Center, San Francisco, CA, US; 3 University of California San Francisco, San Francisco, CA, US

Background: HIV-infected individuals are at increased risk for atherosclerosis. The underlying mechanisms may include alterations in gut microbial flora, leading to immune activation. Trimethylamine-N-oxide (TMAO) is metabolized by intestinal microbiota from dietary lipids. In uninfected persons, TMAO levels are associated with cardiovascular events. The objective of this study was to investigate factors associated with TMAO and determine if TMAO is associated with subclinical atherosclerosis in HIV-infected individuals. Methods: TMAO levels in 83 HIV-infected individuals were compared to an external cohort of uninfected individuals referred for cardiac catheterization for suspected coronary artery disease (CAD) from Tang et al (NEJM 2013; 368:1575-1584). Carotid intima-media thickness (IMT) was assessed using high resolution ultrasound. Multivariable analysis was performed to identify the relationship between TMAO and mean IMT. Results: Compared to controls, the HIV group was younger (50 ± 10 vs 63 ± 11 yrs), primarily male (94% vs 64%), and had lower rates of DM (11% vs 32%) and HTN (46% vs 72%). Nearly 75% of the HIV cohort were on anti-retroviral therapy (ARVs). Median TMAO level in the HIV cohort was 3.7 m M (IQR 2.5-6.3), which was identical to that in uninfected controls with CAD (3.7, IQR 2.4-6.2). In adjusted analysis, age, cigarette smoking, triglycerides, and current ARV use were independently associated with higher TMAO levels in the HIV group. Viral load and CD4 count were not associated with TMAO levels. The mean carotid IMT was 0.105 ± 0.035 mm in HIV-infected individuals. TMAO per doubling was associated with 9% greater mean carotid IMT in univariate analysis (p=0.002), but the association weakened in the adjusted model (+4%, p=0.14). Age, Latino/Asian race, HTN, cigarette smoking, total cholesterol, and lipodystrophy were also associated with greater IMT. Conclusions: Despite being younger and having fewer traditional risk factors, HIV-infected patients had similar TMAO levels as uninfected individuals with CAD. While viral load and CD4 count were not predictive of higher TMAO levels, current ARV use was. In conclusion, these results suggest that TMAO levels are elevated and may be associated with mean carotid IMT in HIV-infected individuals. Future studies will need to establish whether these elevated circulating TMAO levels in HIV patients are associated with an increased risk of cardiovascular events. 756 Impaired Cardiac Strain and Biomarkers of Immune Activation in HIV Colleen Hadigan 1 ; Julia Purdy 1 ; DianaThiara 1 ; Louisa Howard 1 ; Chia-Ying Liu 1 ; Fabio Raman 1 ; Sabrina Mangat 1 ; Christopher Sibley 2 ; David Bluemke 1 1 National Institutes of Health (NIH), Bethesda, MD, US; 2 Oregon Health and Sciences University, Portland, OR, US Background: Chronic HIV infection is associated with an increased risk of cardiovascular disease (CVD). Subclinical cardiac dysfunction can be assessed through MRI measurements of cardiac strain and myocardial fibrosis. In order to investigate the underlying etiology of CVD in HIV, we performed cardiac MRI in conjunction with biomarkers of inflammation and immune activation in a cohort of HIV+ adults without known CVD. Methods: This is a prospective cross-sectional study of 95 HIV+ adults and 30 age, sex, race-matched healthy controls. Myocardial fibrosis (quantified as extracellular volume index) and regional cardiac strain were measured by MRI. Laboratory determinations included serologic biomarkers of inflammation, coagulation, and immune activation (e.g. C-reactive protein [CRP], D-dimer, pro-brain natriuretic peptide [pro-BNP], monocyte chemoattractant protein-1 [MCP-1], lipopolysaccharide binding protein [LBP], tissue inhibitor of metalloproteinase-1 [TIMP-1]). Results: Radial strain and epicardial-endocardial circumferential strain were significantly decreased in HIV+ compared to controls (Table 1). Among the HIV+ group, radial strain impairment was strongly correlated with increased levels of MCP-1 (r=-0.43, p<0.0001), pro-BNP (r=-0.28, p<0.01), TIMP-1 (r=-0.28 p=0.009) and LBP (r=-0.21, p=0.03). In a multivariable regression adjusting for smoking and age, HIV status (p=0.04) and increased MCP-1 levels (p=0.0002) remained significant independent predictors of impaired radial strain. Myocardial fibrosis was also increased in the HIV+ group compared to controls, and correlated with decreased epicardial-endocardial circumferential strain (r=0.22, p=0.03).

Poster Abstracts

Conclusions: HIV-infected subjects demonstrate subclinical impairment in systolic function and this is associated with markers of chronic immune activation, inflammation and tissue remodeling. Similar to patients with chronic heart failure, increased levels of MCP-1, a chemokine important in the regulation of macrophage migration and a marker of immune activation, was a strong independent predictor of impairment in cardiac function. LBP, an acute phase protein made in response to LPS, and TIMP-1, a marker of tissue remodeling, were also associated with impaired cardiac strain. Our findings indicate that subclinical impairment in cardiac strain tracks with markers of chronic inflammation and immune activation, which may serve as targets for future therapeutic strategies to optimize long-term cardiovascular health in persons living with HIV.

464

CROI 2015