CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

SAT CD4 T cells, potentially reflecting a link between accumulation of adipose resident CD4 cells and metabolic disease.

685 FIBROBLAST GROWTH FACTOR 21 (FGF21) IS ELEVATED IN HIV AND AFFECTED BY INFLAMMATION Allison Ross Eckard 1 , Mary Ann O’Riordan 2 , Danielle Labbato 2 , Julia C. Kosco 2 , Vanessa El Kamari 2 , Grace A. McComsey 2 1 Medical University of South Carolina, Charleston, SC, USA, 2 Case Western Reserve University, Cleveland, OH, USA Background: FGF21 is a relatively recently identified endocrine hormone that appears to have beneficial metabolic effects, including promoting weight loss, improving glucose metabolism and decreasing inflammation. In obesity, diabetes and metabolic syndrome, FGF21 levels are paradoxically increased, suggesting an FGF21-resistant state. Levels in HIV have been related to metabolic abnormalities, but little is known about FGF21 and its relationship to HIV-specific vs. non-HIV factors. Methods: HIV+ subjects on antiretroviral therapy (ART) or naïve to therapy were prospectively enrolled, along with healthy controls and underwent a comprehensive clinical and laboratory assessment. Body composition was assessed by dual-energy x-ray absorptiometry. Fasting lipids, insulin, glucose, and inflammatory markers were measured. Plasma FGF21 levels were assessed in duplicate by ELISA and log-transformed to achieve a normal distribution. Results: 150 HIV+ (119 on ART; 31 ART-naïve) and 29 controls were enrolled. There was no significant difference in age-adjusted log FGF21 (pg/mL) between subjects on ART vs. ART-naïve (5.4 vs. 5.3; P=0.68), so groups were combined and compared to controls. There was no difference between HIV+ and controls in sex, race, alcohol use, body mass index (BMI), trunk fat, and HDL-C, but HIV+ were older with more smokers and higher waist-to-hip ratio (WHR), waist circumference (WC), HOMA-IR, LDL-C, and triglycerides (TG). Unadjusted log FGF21 was higher in HIV+ vs. controls (5.4 vs. 4.8; P=0.003). After controlling for age, smoking and alcohol use, log FGF21 remained higher in HIV+ (5.3 vs. 4.9; P=0.04). In HIV+, variables most associated with higher FGF21 in bivariate analyses included older age, smoking, alcohol use, increased trunk fat, WHR, WC, TG, HOMA-IR, IL-6, sTNFR-I, viral load >200 copies/mL, and lower LDL-C. Other HIV variables (nadir/current CD4, HIV duration, ART duration/type), BMI, sex, and race showed no relationship to FGF21. In stepwise regression models, variables that affected FGF21 most significantly were smoking, higher IL-6 and TG, and lower LDL-C. Conclusion: People with HIV, regardless of treatment, have increased circulating FGF21 compared to healthy controls. Inflammation appears to play a significant role in affecting FGF21 in HIV, whereas other aspects of HIV/ART do not. Further research is needed to determine the role that inflammation plays in FGF21 pathways and whether increased FGF21 levels are due to a resistant state or reflect a compensatory response. 686 HAART IS ASSOCIATED WITH REDUCED RISK OF OSTEOPOROSIS-RELATED FRACTURES José A. Barletta, Monica Ye, Michelle Lu, Mia Kibel, Viviane D. Lima , Oghenowede Eyawo, Julio S. Montaner, Robert S. Hogg, Silvia Guillemi British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada Background: People living with HIV (PLWHIV) face a higher risk of osteoporosis-related fractures (ORF) compared with HIV-negative individuals. HIV-related systemic inflammation and antiretroviral therapy (ART), particularly tenofovir disoproxil fumarate (TDF), have been associated with reduced bone mineral density; however, there is no clear association between ORF and these factors. We investigated the association of HIV-related factors including viral suppression and ART exposure with the risk of ORF among PLWHIV in British Columbia, Canada (BC). Methods: Our study uses data from the Comparative Outcomes and Service Utilization Trends (COAST) study, a population-based retrospective cohort study

Poster Abstracts

684 ADIPOSE TISSUE CD4+ AND CD8+ T-CELL PROFILES DIFFER BY GLUCOSE TOLERANCE IN HIV Celestine Wanjalla , Wyatt J. McDonnell, Louise L. Barnett, Joshua Simmons, Briana Furch, Morgan Lima, Beverly O. Woodward, Mark Pilkinton, Nancy J. Brown, Spyros Kalams, Simon Mallal, John R. Koethe Vanderbilt University, Nashville, TN, USA Background: T lymphocytes play a central role in modulating adipose tissue inflammation and, by extension, adipocyte function. We hypothesized that greater adipose tissue T-cell activation in persons living with HIV (PLWH) may contribute to higher rates of diabetes. Methods: We compared CD4 and CD8 T-cell subsets in the subcutaneous adipose tissue (SAT) and blood of 9 non-diabetic (fasting blood glucose [FBG]<100mg/dL), 8 pre-diabetic (FBG=100-125 mg/dL) and 9 diabetic (FBG>=126mg/dL) PLWH, in addition to 8 pre-diabetic, HIV-negative [HIV(-)] controls. SAT was collected by liposuction and T cells extracted by collagenase digestion. The proportion of naïve (TN) CD45RO-CCR7+, effector memory (TEM) CD45RO+CCR7−, central memory (TCM) CD45RO+CCR7+, and effector memory revertant RA+ (TEMRA) CD45RO-CCR7− CD4 and CD8 T cells were measured by flow cytometry. T cell subsets were compared by Wilcoxon signed-rank (paired blood and adipose), Mann-Whitney (between groups), and linear regression tests according to glucose tolerance. Results: Age, race and sex were similar across groups. Compared to HIV(−) controls, SAT from PLWH with similar glucose tolerance had significantly higher CD8 T cells (49% vs 19%, p<0.01) and lower CD4 T cells (47% vs 65%, p<0.01). The distribution of SAT CD4 and CD8 memory subsets did not differ by HIV status, except for higher CD4 TCM (p<0.01) and lower CD4 TEM (p<0.05) in the PLWH. SAT was enriched for CD4 TEM compared to blood (45 vs. 15%, p<0.0001) and TEMRA (8 vs. 2%, p<0.0001), depleted in TN (16 vs. 29%, p<0.001) and TCM (15 vs. 26%, p<0.001). These findings were similar for CD8 T cell subsets. While the relative proportions of SAT CD4 and CD8 TCM, TEM, and TEMRA cells were similar regardless of glucose tolerance status in PLWH, expression of CD69 - a marker of activation and tissue resident cells - on CD4 T cells rose with progressive insulin resistance (see Table, p=0.004), which was robust to adjustment for BMI (p=0.03). Among CD4 T cell subsets, progression from non-diabetic to diabetic groups was accompanied by increased CD69 on TCM, TEM, and TEMRA cells. Conclusion: This study is the first to characterize SAT CD4 and CD8 memory T cell subsets in PLWH. SAT from PLWH is enriched for TEM and TEMRA CD4 and CD8 compared to blood, which could contribute to tissue inflammation. Increased insulin resistance in PLWH is associated with increased CD69 on

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