CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

does not modify blood flow but predisposes arterioles to thrombosis in the presence of other deleterious vascular agents. In contrast, higher concentrations of ferric chloride (over 75 mM) induced thrombi by themselves, an effect that was maintained in leukopenic mice. Images were recorded until blood flow ceased or for 8 min if no vessel occlusion occurred. Results: ABC induced dose-dependent vessel occlusion in non-leukopenic mice following superfusion with 25 mM ferric chloride (Figure 1). Rofecoxib – a well characterized vascular deleterious agent - generated levels of thrombosis similar to those produced by ABC when administered in the same setting. However, while the pro-thrombotic effects of rofecoxib were maintained in leukopenic mice, those of ABC were absent. Conclusion: The pro-thrombotic effect of ABC in vivo depends on the presence of leukocytes, thus demonstrating a key role of these cells in the deleterious vascular effects of this drug. These results support previous research suggesting that ABC induces thrombi formation through a specific mechanism involving leukocyte purinergic P2X7 signalling. This may explain the cardiovascular toxicity associated with the use of ABC in humans.

Wilcoxon rank sum tests were used for between and within-group comparisons and Spearman’s correlation for bivariate associations. Results: HIV+ and HIV- groups were well matched (Table) with HIV+ subjects reassessed 17 [13, 18] months post viral suppression with ART (80% TDF/ FTC+NNRTI). HEC increased in the HIV+ group after ART initiation (+7.85 [3.47, 17.5]%, p=0.007) approaching levels similar to HIV- controls (p=0.776). Increases in HEC correlated with decreases in HDLox (r=-0.509, p=0.02) and increases in HDL cholesterol (r=+0.545, p=0.013) but not with changes in MCE (r=-0.066, p=0.782). Notably, in the HIV- group, higher HEC correlated with lower MCE (r=-0.61, p=0.004) while in the HIV+ group post-ART, higher HEC correlated with higher MCE (r=+0.499, p=0.025). Changes in HEC were not affected by gender, race, smoking, age, pre-ART HIV RNA, lipids or T cell parameters. Conclusion: ART initiation is accompanied by increases in HEC and reductions in HDLox to levels seen in HIV- controls, suggesting improvements in HDL function with ART. However, divergent associations between HEC and MCE in the HIV- and HIV+ groups, together with enhanced MCE post-ART indicate ongoing dysregulation of RCT at the M/M cellular level in treated PLWH.

Poster Abstracts

676 FUNCTIONAL STATUS ASSOCIATED WITH CARDIOVASCULAR DISEASE AND DIABETES IN HIV+ ADULTS Sean G. Kelly 1 , Kunling Wu 2 , Katherine Tassiopoulos 2 , Kristine M. Erlandson 3 , Susan L. Koletar 4 , Frank J. Palella 5 1 Vanderbilt University, Nashville, TN, USA, 2 Harvard University, Cambridge, MA, USA, 3 University of Colorado Denver, Denver, CO, USA, 4 The Ohio State University, Columbus, OH, USA, 5 Northwestern University, Chicago, IL, USA Background: Age-related frailty and disability contribute to mortality and occur earlier in HIV+ persons, however their associations with other age-related chronic diseases remain unknown. We evaluated associations between frailty and disability and incident non-AIDS related clinical events among participants enrolled in AIDS Clinical Trials Group (ACTG) A5322. Methods: At A5322 entry, we performed functional status assessments by measuring frailty by Fried’s criteria and disability by impairment in Instrumental Activities of Daily Living (IADL). We recorded incident cardiovascular events (CVE: coronary artery disease, myocardial infarction, angina, stroke, cardiomyopathy, peripheral arterial disease, systolic heart failure, arrhythmia, deep vein thrombosis, pulmonary embolism) and diabetes (DM). Multivariable Poisson regression assessed associations between frailty, disability, CVE and DM, as well as effect modification by demographic variables on these associations. Results: Among 1035 HIV+ participants, all aged ≥40 years, 81%were male, 48%were white, non-Hispanic, 29%were black, non-Hispanic, 46% were pre-frail or frail, and 17% had disability. Median age was 51 years and median duration of follow-up was 3.3 years. Forty-nine CVE were observed. Among black, non-Hispanic persons, being pre-frail/frail was associated with substantially increased risk of CVE (adjusted rate ratio [RR] 5.24, 95% C.I.=1.52,18.1) while being pre-frail/frail was not associated with CVE among persons of other race/ethnicity (white, non-Hispanic: RR=1.40, 95%

675 EXPLORING CHANGES IN HDL AND MONOCYTE CHOLESTEROL METABOLISMWITH ART INITIATION

Robert T. Maughan 1 , Jane A. O’Halloran 1 , Alejandro A. Garcia 1 , Theodoros Kelesidis 2 , Luke O’Brien 1 , John Lambert 1 , Gerard Sheehan 3 , Patrick W. Mallon 1 1 University College Dublin, Dublin, Ireland, 2 University of California Los Angeles, Los Angeles, CA, USA, 3 Mater Misericordiae University Hospital, Dublin, Ireland Background: Dysregulated reverse cholesterol transport (RCT) may contribute to cardiovascular disease pathogenesis in people living with HIV (PLWH). Key components of RCT include cellular cholesterol efflux, the capacity of HDL to accept cholesterol from cells like monocytes/macrophages (M/M) and the oxidative status of HDL (HDLox; increased HDLox reflects impaired HDL function). We previously reported enhanced M/M cholesterol efflux (MCE) and reduced HDLox after antiretroviral therapy (ART) initiation. We aimed to determine how HDLox and MCE interact with HDL efflux capacity (HEC) after ART initiation. Methods: In a prospective cohort study of PLWH before and after ART initiation compared to HIV- controls matched for age, gender, ethnicity, smoking and hepatitis status, HEC was measured by exposing murine macrophages loaded with fluorescently labelled cholesterol to apolipoprotein B (apoB)- depleted plasma from study subjects. HEC was calculated from total cellular (TC) and supernatant (S) cholesterol measures as [(S/TC+S)*100]. MCE was calculated from the ratio of extra to intracellular cholesterol in subjects’ monocytes after exposure to apoA1. HDLox levels were measured using a fluorometric assay normalized to HDL cholesterol. Data are median [IQR]. Mann Whitney and

CROI 2018 251