CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

over-activated and malignant cells, whereas EGF is involved in myocardial protection from acute stress. Combination of IL-32δ with these biomarkers has the potential to better predict CVD in HIV+ individuals. 633 INFLAMMATION-RELATED GENES ARE ASSOCIATED WITH ACCELERATED AGING IN HIV Erin Sundermann 1 , Mariam Hussain 2 , David J. Moore 2 , Steven Horvath 3 , Andrew Levine 3 , for the HNRP Group 1 University of California San Diego, La Jolla, CA, USA, 2 University of California San Diego, San Diego, CA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA Background: Chronic, low-grade inflammation is characteristic of both HIV disease and aging (“inflammaging”), and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether inflammation-related single nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated non-AIDS (HANA) conditions among PLWH. Methods: This was a cross-sectional, observational cohort study that examined 155 HIV+ cases (mean age=47.3, 81%male, 68%White) from the National NeuroAIDS Tissue Consortium. All cases had existing pre-mortem behavioral/ medical/virologic data, post-mortem tissue samples, as well as genetic and epigenomic data. Accelerated aging was measured according to the Epigenetic Clock; a published biomarker of aging based on the relationship between chronological age and biological age as defined by DNA methylation levels of 353 CpGs. The resulting age estimate, DNA methylation age, was related to chronological age. Past or current HANA conditions including cerebrovascular disease, liver disease, kidney disease, COPD, cancer, and diabetes were determined via self-report or extrapolated frommedical records. Mean age acceleration (expressed as Z-scores) and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers separately for each SNP (IL-6 -174G/C, IL-10 -592C/A, TNFα -308 G/A). Statistical analyses were adjusted for relevant demographic and clinical factors including comorbidities (HIV-associated neurocognitive disorder [HAND], lifetime major depressive disorder, substance use disorders, HIV disease characteristics, study site, and DNA methylation assay batch. Results: IL-6 minor allele carriers and IL-10 major allele homozygotes demonstrated significantly greater accelerated aging (higher Z-scores) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ between IL-10 genotype, but was 3.4 times greater in IL-6 minor allele carriers versus others. TNFα genotype was not associated with accelerated aging, nor HANA conditions. Conclusion: SNPs in the interleukin pathway (IL-6 and IL-10) may be helpful in identifying PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may lead to interventional approaches to treat the potential of rapid aging among persons living with HIV. 634 IMPACT OF INFLAMMATION AND GUT IMMUNITY ON CORONARY ARTERIAL WALL COMPOSITION Robert C. Güerri-Fernández 1 , Netanya S. Utay 2 , Zhong-Min Ma 1 , Surinder Mann 1 , Talía Sainz 3 , Marjorie Pion 4 , Alan Landay 5 , Friedrich Knollmann 1 , David M. Asmuth 1 1 University of California Davis, Davis, CA, USA, 2 University of Texas at Houston, Houston, TX, USA, 3 La Paz University Hospital, Madrid, Spain, 4 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 5 Rush University, Chicago, IL, USA Background: Factors that impact CAWC in the setting of HIV disease are poorly understood. We sought to investigate how HIV infection and associated changes in gut immunity, systemic inflammation and initiation of ART impacts coronary CT angiogram (CCTA). Methods: 18 chronic HIV+ ART-naïve patients (pts) underwent CCTA,upper endoscopy for duodenal biopsies (gut) and phlebotomy before and 1 yr after initiating darunavir/ritovavir/ tenofovir disoproxil fumarate/ emtricitabine (ART).17 matched HIV- control (C) underwent identical procedures once. Known cardiovascular disease was exclusionary. Gut samples underwent tissue immunohistochemistry (IHC) or FACS analysis. 3D reconstruction of CCTA of 3 main arteries (RCA, LAD, and LCx) (expressed as % of total artery diameter) and Hounsfield Units using Aquarious iNutrition software.Plasma inflammatory biomarkers were measured by ELISA.Values are expressed as median values [interquartile range] and non-parametric (Spearman’s Rho coefficient (SrC)) were used where appropriate.

632 IL-32Δ AND TRAIL: NEW CARDIOVASCULAR DISEASE BIOMARKERS IN ART-TREATED HIV INFECTION Mohamed El-Far 1 , Madeleine Durand 1 , Carl Chartrand-Lefebvre 1 , Etienne Larouche-Anctil 1 , Sarah M. Zaidan 1 , Genevieve Chabot-Roy 2 , Rémi Bunet 1 , Mohamed Sylla 1 , Jean-Guy Baril 1 , Petronela Ancuta 1 , Sylvie Lesage 3 , Nicolas Chomont 1 , Robert C. Kaplan 4 , Alan Landay 5 , Cécile L. Tremblay 1 , for the The Canadian HIV and Aging Cohort Study 1 Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada, 2 Centre de recherche Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada, 3 Université de Montréal, Montreal, QC, Canada, 4 Albert Einstein College of Medicine, Bronx, NY, USA, 5 Rush University Medical Center, Chicago, IL, USA Background: We recently demonstrated that enhanced expression of IL-32δ, a regulatory isoform of the proinflammatory cytokine IL-32, positively correlates with the coronary artery atherosclerotic total plaque volume (TPV), a subclinical cardiovascular disease (CVD) marker in HIV+ individuals receiving anti- retroviral therapy (ART). Here, we screened for new biomarkers associated with subclinical CVD that in combination with IL-32δ may serve to better predict CVD susceptibility/progression. Methods: Plasma was collected from n=52 ART-treated aviremic HIV+male participants with no clinical CVD from the Canadian HIV and Aging Cohort Study and n=23 age-matched uninfected controls. Participants prospectively underwent contrast-enhanced cardiac computed tomography and TPV measurement. HIV+ group was divided into n=30 with subclinical coronary artery atherosclerosis (TPV>0) and n=22 without (TPV=0) (median CD4 count: 593 and 581 cells/mm3 and median age: 53.3 and 50.5 years, respectively). Soluble factors were quantified by Luminex assay and selected biomarkers validated by ELISA. Expression of IL-32 mRNA was quantified by SYBRGreen RT-PCR in peripheral blood mononuclear cells. Results: Expression of IL-32δ in HIV+ participants with atherosclerotic TPV was 1.5fold higher compared to TPVneg individuals (mean±SD: 0.038±0.017 vs 0.025±0.018, p=0.0006). Among 38 analytes measured by Luminex assays, levels of TNF-related apoptosis inducing ligand (TRAIL) and Epidermal Growth Factor (EGF) were lower in plasma from TPV+ compared to TPVneg HIV-infected individuals (68.5±24.3 vs 85.3±23.1 pg/ml for TRAIL and 694.1±269 vs 906.4±256.5 pg/ml for EGF, p=0.04 and p=0.01, respectively). Interestingly, IL-32δ mRNA expression negatively correlated with TRAIL (Spearman r=-0.30, p=0.032) and showed a trend for a negative correlation with EGF (Spearman r=-0.25, p=0.076). Similarly, plasma IL-32 levels negatively correlated with TRAIL (Spearman r=-0.31, p=0.024). Age, smoking or lipid levels did not confound these results. Conclusion: Our study reveals that high expression of IL-32δ in blood cells of ART-treated HIV+ individuals with subclinical CVD correlated with low plasma levels of TRAIL and EGF, two emerging biomarkers of CVD that likely play atheroprotective roles. Indeed, TRAIL was shown to induce cell death of

Poster Abstracts

CROI 2019 240