CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Background: Persons with HIV (PWH) are at increased risk for heart failure (HF) compared with uninfected persons but few studies have evaluated whether this risk varies by severity of HIV infection. Methods: We conducted an observational cohort study of adults (age ≥21 years) with and without HIV, frequency-matched 1:10 by age, sex, race/ ethnicity, primary medical facility and calendar year, who were members of Kaiser Permanente in Northern California, Southern California, Maryland, D.C. or Virginia between 2000 and 2016. Patients’ electronic health records were reviewed to determine incident HF (either preserved or reduced left ventricular systolic function). Using Poisson regression, we estimated relative risk (RR) of incident HF by HIV status overall, and by HIV status with PWH stratified by recent CD4 count, nadir CD4 count, or HIV RNA level, with laboratory measures lagged by 6 months (i.e., at least 6 months prior to HF assessment). We adjusted for sociodemographic characteristics (sex, current age, race/ethnicity, socioeconomic status) and risk factors for HF, including BMI>25, antecedent acute myocardial infarction, hypertension, diabetes mellitus, dyslipidemia, ever documented history of smoking, alcohol use disorder and drug use disorder. Results: The study included 38,868 PWH and 386,569 matched uninfected persons (average age 41 years at start of follow-up; 88%male; 38%White, 20% Hispanic, 21% Black). There were 414 HF cases among PWH and 3,298 HF cases among uninfected comparators (0.23 and 0.15 cases of HF per 100 person-years, respectively). Risk of HF was higher overall in PWH (vs. uninfected persons, adjusted RR 1.34, 95% CI: 1.21-1.49). However, when evaluating HF by HIV severity, heightened HF risk was observed only among PWH with lower recent CD4, lower nadir CD4 and higher HIV RNA level (Table). PWH with recent CD4≥500, nadir CD4≥200 and HIV RNA level ≤200 did not have significantly higher risk of HF compared with uninfected persons. Conclusion: Higher HIV viremia and lower CD4 cell count (both recent and nadir) are associated with elevated HF risk. Our data suggest that, in addition to addressing cardiovascular risk factors, earlier HIV diagnosis and treatment, and adherence to antiretroviral therapy, are strategies to prevent HF in PWH.

participating in the Canadian HIV and Aging Cohort Study (n=49 CVD+ with coronary artery atherosclerosis measured by cardiac computed tomography and n=30 CVD-) and HIVneg controls (n=25 CVD+ and n=24 CVD-). We used a generalized linear regression algorithm (glmnet) with Lasso regularization and Leave-One-Out cross validation to predict the presence of coronary artery atherosclerosis in the study participants. Results: Alongside with the upregulation of IL-32D, we observed an HIV-specific signature characterized by higher plasma levels of IL-18, VEGF-A, FGF23, FLT3L and FSH in HIV+ individuals with CVD (univariate analysis, p=0.0016, 0.0053, 0.0386, 0.0075 and 0.049, respectively) combined with lower levels of TNF- related apoptosis inducing ligand (TRAIL), IFNb and IL-3 (p=0.0149, 0.0093 and 0.0288, respectively). By integrating IL-32D expression with these modulated factors in a multivariate analysis, CVD was predicted as a binary outcome (presence/absence) with a misclassification error of 34%. The prediction model was independent of age, statin treatment and smoking. Given the growing evidence for the atheroprotective role of TRAIL-expressing monocytes, we tested the functional link between IL-32 and TRAIL. We show here that primary human monocytes treated with IL-32 down-regulate TRAIL expression, acquire an M1 activated phenotype (CD206negCD163negCD80+TRAILneg) and produce inflammatory cytokines such as IL-6 and TNFα. Conclusion: Here we report a specific plasma inflammatory signature that holds promise to predict CVD in HIV+ individuals independently of traditional risk factors. Moreover, the functional link between IL-32 and TRAIL and their opposite effects on monocyte functions further highlight the key role of IL-32 in CVD and its potential as a therapeutic target in HIV infection. 648 ASSOCIATION OF INFLAMMATORY MARKERS WITH CARDIAC INDICES IN THE MACS Bethel Woldu 1 , Henrique Doria De Vasconcellos 1 , Joseph B. Margolick 2 , Heather McKay 2 , Jared Magnani 3 , Matthew J. Feinstein 4 , Roger Detels 5 , Todd T. Brown 1 , Sean Altekruse 6 , Joao Lima 1 , Katherine Wu 1 , Wendy Post 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA, 4 Northwestern University, Chicago, IL, USA, 5 University of California Los Angeles, Los Angeles, CA, USA, 6 National Heart, Lung, and Blood Institute, Bethesda, MD, USA Background: People living with HIV (HIV+) are at increased risk of heart failure even after adjustment for demographics and cardiovascular risk factors. Among HIV+ without symptoms of heart failure, diastolic dysfunction has been reported to be highly prevalent. We hypothesized diastolic dysfunction to be an early marker of myocardial disease related to heightened inflammation in HIV infection. Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective observational cohort with both HIV+ and HIV-uninfected (HIV-) participants. We evaluated the association of echocardiographic parameters of left ventricular (LV) structure, systolic and diastolic function, and left atrial (LA) volumes to biomarkers of systemic inflammation and coagulation (CRP, IL-6, TNF-alpha and D-dimer). Associations between cardiac indices, biomarker quintiles and HIV serostatus were evaluated with multiple linear regression analyses after multivariable -adjustment for demographics and cardiovascular risk factors (body mass index, systolic blood pressure, hyperlipidemia and diabetes). Results: We included HIV+ (n=384) and HIV- (n=254) men who had both echocardiograms and inflammatory markers in the analysis. HIV+men were younger (age, 59.2 ±6.7 vs 62.5 ±7.5 years, p< 0.001), had similar systolic blood pressure (129 vs 131 mmHg, p<0.24 ) and body mass index (26.8 vs 27.3 kg/m 2 , p<0.20). In multivariable-adjusted models (Table), there was a progressive association of LA volume index with increasing D-dimer quintiles and association with highest IL-6 quintile, independent of HIV serostatus. There were no significant associations between inflammatory markers and echo- derived parameters of diastolic function including transmitral flow velocity (E), mitral annular velocity (e') and E/e’ ratio. Conclusion: In this analysis of HIV+ and HIV- men, larger LA size was associated with markers of heightened systemic inflammation, regardless of HIV serostatus. As left atrial dilation predicts future risk of atrial fibrillation and stroke, further investigation is needed to evaluate whether systemic inflammation mediates increased atrial arrhythmic risk among both HIV+ and HIV- people.

Poster Abstracts

647 PLASMA INFLAMMATORY BIOMARKER SIGNATURE ASSOCIATED WITH CVD IN HIV INFECTION Mohamed El-Far 1 , Madeleine Durand 1 , Carl Chartrand-Lefebvre 1 , Rémi Bunet 1 , Hardik Ramani 2 , Jean-Guy Baril 1 , Benoit Trottier 1 , Samer Mansour 1 , Ali Filali 1 , Petronela Ancuta 1 , Nicolas Chomont 1 , Robert C. Kaplan 3 , Alan Landay 4 , Cécile Tremblay 1 , for the Canadian HIV and Aging Cohort Study (CHACS) 1 Centre de Recherche du CHUM, Montreal, QC, Canada, 2 Montreal Neurological Institute, Montreal, QC, Canada, 3 Albert Einstein College of Medicine, Bronx, NY, USA, 4 Rush University, Chicago, IL, USA Background: We have recently shown that a specific isoform of the human proinflammatory cytokine IL-32 (IL-32D) is selectively upregulated in HIV+ individuals with cardiovascular disease (CVD). Here we extend our studies to screen for other inflammatory markers that could be combined with IL-32 to enhance the prediction of CVD in HIV infection. Methods: Using the MesoScale Technology, we measured 84 inflammatory and anti-inflammatory factors in plasma from n=79 HIV+ aviremic males

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