CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Background: Trimethylamine-N-oxide (TMAO) is a choline metabolite generated from TMA which is produced by gut microbiota. TMAO may promote atherosclerosis and cardiovascular disease (CVD). Yet, the relationships of plasma TMAO and other choline metabolites with progression of atherosclerosis in HIV-infected (HIV+) individuals remain unclear. Methods: Plasma TMAO, choline, betaine, dimethylglycine, and sarcosine were measured among 520 HIV+ and 217 HIV-uninfected (HIV-)participants from WIHS (398 women) and MACS (339 men). Progression of carotid atherosclerosis was assessed by repeated B-mode carotid artery ultrasound imaging from2004–2013.Poisson regression models were used to examine associations of choline metaboliteswith incident carotid artery plaque (focal intima-media thickness >1.5 mm) over 7 years (all participants without carotid plaque at baseline). Results: Median ages were similar between HIV+ and HIV- groups (42 years in women and 46 years in men); In the HIV+ group, 74% of women and 83% of men used potent ART, and 46% of women and 66% of men had undetectable HIV-1 viral load(≤80 copies/mL).Over 7 years, 112 individuals (90 HIV+ and 22 HIV-) developed incident carotid artery plaque (focal intima-media thickness >1.5 mm).There was no significant difference in plasma TMAO or other choline metabolite levels between HIV+ andHIV- groups. After multivariate adjustment, higher plasma TMAO was significantly associated with increased risk of incident carotid artery plaque in HIV+individuals(risk ratio=1.22 [95% CI, 1.03-1.46] per standard deviation increment; P=0.02), but not in HIV- individuals (Table). However, there was no significant effect modification by HIV infection. The results were consistent between HIV+ women and men, and across subgroups stratified by HIV related parameters (e.g., viral suppression status). No significant associations between other choline metabolites and incident carotid artery plaque were observed.Plasma TMAO was positively correlated with serumsCD14 and sCD163, biomarkers of monocyte and macrophageactivation and inflammation, but had little correlation withIL-6, CRP or CVD risk factors (blood pressures, lipids, body mass index). Conclusion: Among HIV+ individuals, plasma TMAO, rather than other choline metabolites, is associated with greater progression of carotid artery atherosclerosis. The association between TMAO and monocyte and macrophage activation markers suggests foam cell formation as a potential link of TMAO with atherosclerosis.

persistent inflammation and disease progression. As chronic inflammation is associated with high prevalence of cardiovascular diseases (CVDs) in HIV- infected individuals, we investigated the potential use of specific IL-32 isoforms as biomarkers for CVD. Methods: Blood was collected from 800 participants living with HIV and 200 control subjects from the Canadian HIV and Aging Cohort Study. Overt CVD and complete medical history is recorded prospectively. A subgroup of participants without overt CVD (n=200) undergoes cardiac computed tomography with injection of contrast media and measurement of total atherosclerotic coronary plaque volume. Baseline plasma levels of total IL-32 (pool of all IL-32 isoforms) were measured by ELISA in all participants. To distinguish between different IL-32 isoforms, we developed a quantitative isoform-specific SYBR Green RT-PCR to quantify single isoforms in peripheral blood mononuclear cells (PBMCs). Results: Total plasmatic IL-32 protein was significantly higher in HIV+ ART-treated individuals compared to HIV- participants (median 384 pg/ml vs 287, respectively, p=0.0001). Interestingly, sex and age were associated with differential levels of IL-32; women under the age of 50 had significantly higher levels of IL-32 compared to their counterparts over 50 (p=0.016), whereas the opposite was observed in men. At the transcriptional level, all IL-32 isoforms were highly expressed in PBMCs from HIV+ individuals compared to non-infected controls (p=0.005). In individuals with cardiovascular imaging, the ratio between the delta and beta isoforms (δ/β ratio), positively and significantly correlated with the total atherosclerotic plaque volume (n=60 subjects with coronary atherosclerosis and n=26 subjects without, p=0.02, Spearman r=0.36). Of note, IL-32δ is known to bind to IL-32β and inhibits its anti-inflammatory functions. Conclusion: Our data suggest a protective role for IL-32β in CVD but a deleterious role for IL-32δ. Furthermore, our study shows for the first time that the ratio IL-32δ/IL-32β may be used as a predictive biomarker for coronary plaque formation and CVD in HIV+ individuals on ART. 710 INTEGRATED VS REFERRED MANAGEMENT OF CVD RISK FACTORS FOR HIV+ PATIENTS IN SWAZILAND Miriam Rabkin 1 , Anton M. Palma 1 , Margaret McNairy 2 , Samkelo Simelane 3 , Averie B. Gachuhi 1 , Raymond A. Bitchong 4 , Harriet Nuwagaba-Biribonwoha 3 , Pido Bongomin 3 , Velephi Okello 5 , Wafaa M. El-Sadr 1 1 ICAP at Columbia University, New York, NY, USA, 2 Weill Cornell Medicine, New York, NY, USA, 3 ICAP at Columbia University–Swaziland, Mbabane, Swaziland, 4 Raleigh Fitkin Memorial Hospital, Manzini, Swaziland, 5 Ministry of Health, Mbabane, Swaziland Background: Cardiovascular disease risk factors (CVDRF) are prevalent in HIV-positive (HIV+) persons, but the optimal model for managing patients with both HIV and CVDRF in low-resource settings is unknown. We compared integrated vs. referred CVDRF management for adults on antiretroviral therapy (ART) in Swaziland. Methods: HIV+ persons ≥40 years on ART were screened for hypertension (HTN), diabetes (DM), hyperlipidemia (HL) and tobacco use. Those with HTN and/ or >10% ten-year CVD risk (by WHO/ISH risk stratification) were randomized 1:1 to receive CVDRF care at HIV clinic (INT) or at outpatient clinic (REF). Primary outcomes were linkage to CVDRF care within 1 month and retention in both CVDRF and HIV care at 6 months. Other outcomes were: number of visits, adherence with assigned study arm, medication initiation, systolic blood pressure (SBP), HbA1c, and total cholesterol (TC). Results: 240 participants (pts) were enrolled (Table). Median age was 51 years, 66%were female, 97% had HTN, 17% had DM and 14% had HL; baseline characteristics were similar in both arms. Linkage to CVDRF care within 1 month was achieved by 85% and 84% of pts in the INT and REF arms, respectively. Pts in both arms attended 2.8 CVDRF visits on average; those in the INT arm were more likely to adhere to their assigned study arm (86% vs . 68%, risk ratio [RR]: 1.28). At 6 months, retention in HIV care was high (98%) but retention in CVDRF care was low (21%) with no differences between arms. Despite limited retention in CVDRF care, 122/193 (63%) of pts with HTN initiated anti- hypertensive medicines; this was more likely in the INT arm (72% vs . 53%, RR: 1.35). Reductions in SBP and HbA1c occurred equally in both arms. Compared to baseline, mean ΔSBP was -15.0 mmHg (confidence interval [CI] -18.0, -11.8) in the INT arm and -15.9 mmHg (CI -19.0, -12.8) in the REF arm; mean ΔHbA1c was -0.68% (CI -1.26, -0.10) and -1.37% (CI -2.51, -0.24) in the INT and REF arms, respectively. Pts with HL in the REF arm also achieved significant reduction in TC (-0.91 mmol/L, CI -1.76, -0.65); there was no significant ΔTC in the INT arm.

Poster Abstracts

709 IL-32 ISOFORMS AS NOVEL BIOMARKERS FOR CVD IN HIV-INFECTED INDIVIDUALS Mohamed El-Far 1 , Sarah M. Zaidan 1 , Carl Chartrand-Lefebvre 1 , Petronela Ancuta 1 , Nicolas Chomont 1 , Etienne Larouche-Anctil 1 , Jean-Pierre Routy 2 , Benoit Trottier 3 , Jean-Guy Baril 1 , Paul MacPherson 4 , Sylvie Trottier 5 , Robert C. Kaplan 6 , Alan Landay 7 , Madeleine Durand 1 , Cécile Tremblay 1 1 Centre de Research du Centre Hospitalier de l’Université de Montreal, Montreal, QC, Canada, 2 McGill University Health Centre Research Institute, Montreal, QC, Canada, 3 Clinique Médicale l’Actuel, Montreal, QC, Canada, 4 Ottawa General Research Institute, Ottawa, ON, Canada, 5 Centre Hospitalier de l’Université Laval, Quebec, QC, Canada, 6 Albert Einstein College of Medicine, Bronx, NY, USA, 7 Rush University Medical Center, Chicago, IL, USA Background: Human il32 gene encodes for multiple IL-32 isoforms known to exhibit distinct immune-regulatory potential: proinflammatory (α and γ), anti-inflammatory (β), and regulatory (δ). The contribution of these isoforms to infectious and inflammatory diseases is poorly understood. We have recently reported that overexpression of total IL-32 in HIV infection correlates with

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