CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

674 GUT INTEGRITY MARKERS AND ASSOCIATIONS WITH ADIPOSITY IN PEOPLE WITH AND WITHOUT HIV Allison Ross Eckard 1 , Carlee Moser 2 , Judith S. Currier 3 , Todd T. Brown 4 , Emily Bowman 5 , Peter W. Hunt 6 , Nicholas Funderburg 5 , Grace A. McComsey 7 1 Medical University of South Carolina, Charleston, SC, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 The Ohio State University, Columbus, OH, USA, 6 University of California San Francisco, San Francisco, CA, USA, 7 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: Fat accumulation after ART initiation remains a serious problem in people with HIV (PWH), but little is known about its pathogenesis. Gut barrier dysfunction may play a role, but data are inconsistent and lack adequate control groups. We compared gut integrity markers in PWH before and after ART to an uninfected control group and assessed associations between gut integrity markers and body composition. Methods: Data from uninfected controls (matched by age, sex, and race) were prospectively collected and compared to data from participants prospectively enrolled in a treatment initiation study, ACTG A5260s, at 2 timepoints: pre-ART and 96 weeks after suppressive ART. Plasma levels of gut integrity markers, zonulin, intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP) and beta-D-glucan (BDG), were measured by ELISA. Body composition was assessed by whole-body DXA. Groups were compared using logistic or linear regression with adjustment for matching factors, and associations were assessed using linear regression models. Results: 234 PWH and 116 controls were included. Groups were similar in age and race (PWH: mean 38 yrs, 65%white, non-Hispanic), but PWH included more men (90% vs 80%; P=0.01). PWH pre- and post-ART had significantly higher levels of I-FABP and zonulin (mean difference: 0.37 to 0.59 log 10 pg/mL and 0.54 to 0.56 log 10 ng/mL, resp), but lower levels of LBP (mean difference: 2.65 to 2.66 log 10 ng/mL) vs controls (all P<0.001). PWH had similar levels of BDG pre-ART, but higher levels post-ART vs controls (mean difference: 0.14 log 10 pg/ml, P=0.004). In all models for controls, LBP, I-FABP and BDG showed associations with body composition measures (Table); however, associations with SAT were slightly attenuated when adjusted for sex. In PWH post-ART, I-FABP was significantly associated with outcomes in both unadjusted and adjusted models with effect sizes larger in magnitude than in controls (Table); limited associations were observed with I-FABP at the pre-ART time point. Conclusion: Levels of gut integrity markers, I-FABP and zonulin, were higher in PWH both pre- and post-ART, and BDG was higher in PWH post-ART. Gut integrity markers showed significant associations with several body composition measures in uninfected controls, but the strongest associations were seen with I-FABP among PWH on suppressive ART. I-FABP levels may help predict deleterious fat changes after ART initiation.

673 TELMISARTAN DECREASES MONOCYTE CX3CR1 EXPRESSION IN TREATED HIV INFECTION Jordan E. Lake 1 , Eunice Yeh 2 , Douglas W. Kitch 2 , Anoma Somasunderam 1 , Michael M. Lederman 3 , Judith S. Currier 4 , Netanya S. Utay 1 , for the A5317 Team 1 University of Texas at Houston, Houston, TX, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 Case Western Reserve University, Cleveland, OH, USA, 4 University of California Los Angeles, Los Angeles, CA, USA Background: Telmisartan is an angiotensin receptor blocker and PPAR-g agonist that is active in adipose tissue (AT) and has anti-inflammatory properties. Secretion of fractalkine by adipocytes and expression of its receptor, CX3CR1, on monocytes/macrophages have been implicated in AT inflammation, obesity and cardiovascular disease (CVD). Fractalkine/CX3CR1 expression are mediated by PPAR-g suppression and endotoxemia, both sequelae of HIV. We hypothesized that telmisartan would improve the profile of AT immune cells and AT function in persons with HIV (PWH) on suppressive antiretroviral therapy (ART). Methods: AIDS Clinical Trials Group study A5317 randomized (2:1) PWH >/=18 years old on ART and with HIV-1 RNA <50 copies/mL for >/=48 weeks to receive telmisartan or no drug (controls) for 48 weeks. In a secondary analysis of persons remaining on study drug (if applicable) and ART, maintaining HIV-1 RNA < 200 copies/mL and having subcutaneous AT biopsy samples at weeks 0 and 48, AT immune cell profiling was performed via flow cytometry and IL-6, adiponectin and insulin gene expression determined by PCR array. 48-week changes were compared used two-sided rank-sum, signed-rank tests, and Spearman correlations (a=0.05). Results: Thirty-five participants (22 telmisartan, 13 control) met inclusion criteria; 94%were male and 49%white non-Hispanic. Median age was 49 years and CD4+ T cell count 572 cells/mm 3 . Over 48 weeks, median CD14+16- CX3CR1+monocyte numbers decreased -10.4% in telmisartan-treated PWH, and increased 13.1% in controls (between-group p=0.029). Similar trends were observed for CD14+16+CX3CR1+, CD14lo16+CX3CR1+and CD163+CX3CR1+monocytes (Table). CD14+16-TLR4+monocytes decreased -4.2% in telmisartan-treated PWH vs 0.0% change in controls (between-group p=0.036). Trends were seen for correlations between decreases in CD14+16- CX3CR1+monocytes/increases in insulin gene expression (r=-0.50, p=0.07, n=14), and decreases in CD14+16-TLR4+ monocytes/increases in adiponectin gene expression (r=-0.50, p=0.08, n=13). Conclusion: In PWH on suppressive ART, telmisartan reduced CX3CR1 and TLR4 expression on monocytes, changes that correlated with improved markers of AT function. Given the role of CX3CR1 in AT inflammation, obesity and CVD, telmisartan has the potential to modulate CVD risk in PWH.

Poster Abstracts

675 CONTRIBUTION OF InSTI, BMI, PHYSICAL ACTIVITY, CALORIC INTAKE TO WEIGHT GAIN IN PWH Giovanni Guaraldi 1, Jovana Milic 1 , Andrea Malagoli 1 , Federica Carli 1 , Marianna Menozzi 1 , Alessandro Raimondi 1 , Giacomo Ciusa 1 , Valentina Masi 1 , Michela Belli 1 , Stefano Guaraldi 1 , Cristina Mussini 1 , Todd T. Brown 1 , Jordan E. Lake 2 , Kristine M. Erlandson 3 1 University of Modena and Reggio Emilia, Modena, Italy, 2 University of Texas at Houston, Houston, TX, USA, 3 University of Colorado, Aurora, CO, USA Background: Weight gain in people living with HIV (PWH) is a multifactorial phenomenon in which the relative contribution of traditional and HIV specific modifiable risk factors is not known. The aimwas to assess the population

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