CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

735 LOWER PRETREATMENT GUT INTEGRITY ASSOCIATED WITH FAT GAINS ON ANTIRETROVIRALS Vanessa El Kamari 1 , Carlee Moser 2 , Judith S. Currier 3 , Todd T. Brown 2 , Liz Johnston 2 , Corrilynn O. Hileman 4 , Peter W. Hunt 5 , Grace A. McComsey 6 1 Case Western Reserve University, Cleveland, OH, USA, 2 Harvard University, Cambridge, MA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 MetroHealth Medical Center, Cleveland, OH, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: Despite advances in antiretroviral therapy (ART), obesity and insulin resistance remain a threat to treatment success. HIV infection is known to disrupt gut barrier integrity, leading to microbial translocation. Little is known about the differential effect of integrase and protease inhibitors on gut integrity, and the role of gut dysfunction in metabolic complications associated with ART initiation. Methods: In ACTG A5260, a substudy of A5257, HIV-infected treatment naïve participants were randomized to receive tenofovir-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL) for 96 weeks. Changes in gut integrity markers: intestinal fatty acid binding protein (I-FABP) and zonulin, markers of enterocyte damage and intestinal permeability, respectively, were assessed from baseline to 4, 24, and 96 weeks in all participants that achieved virologic suppression by week 24 and remained suppressed through week 96 on their randomized treatment. Wilcoxon Rank-Sum tests compared changes in gut markers between groups. Linear regression models quantified associations between gut markers, and the following: insulin resistance (by homeostatic model assessment HOMA-IR), BMI, visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT by CT scan) adjusting for baseline age, sex, race/ethnicity, HIV-RNA, CD4 count, smoking, alcohol, drug use, and physical activity. Results: 234 participants included; 90%were male, 48%were white, non- Hispanic. Median age was 36 years, HIV-1 RNA load 4.6 log 10 opies/mL, and CD4 count 338 cells/µL. Overall I-FABP levels increased significantly from baseline throughout 96 weeks (1.7-fold change; 95% CI [1.53,1.78]), without significant difference between arms (p>0.2). Non-significant increases overtime in zonulin levels were observed; zonulin levels were higher in RAL vs DRV/r arm at week 24 (p<0.01), and in RAL vs ATV/r at week 96 (p=0.02). A two-fold higher baseline I-FABP levels were significantly associated with increases in VAT, TAT, and BMI (16%, 9%, 2.5%; p<0.04) over 96 weeks, even after adjusting for confounders. Gut markers levels were not associated with HOMA-IR (p≥0.2). Conclusion: Disruption of gut barrier integrity persists after ART initiation in treatment-naïve participants, regardless of regimen used. Baseline gut dysfunction in ART-naïve individuals is associated with subsequent changes in BMI, total and central fat regardless of regimen used.

Poster Abstracts

734 I-FABP IS ELEVATED AND IS INVERSELY RELATED TO BODY FAT IN HIV Lediya Cheru 1 , Elli Park 1 , Charles Saylor 1 , Kathleen V. Fitch 1 , Tricia H. Burdo 2 , Jake A. Robinson 2 , Martin Torriani 1 , Steven K. Grinspoon 1 , Janet Lo 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 Temple University, Philadelphia, PA, USA Background: Intestinal damage occurs during acute and chronic HIV infection despite suppressive antiretroviral therapy and is posited to be one of the drivers of residual chronic immune activation and inflammation. Our study aims to assess intestinal damage as measured by serum intestinal fatty acid binding protein (I-FABP) to further elucidate its role on body composition in individuals living with HIV. Methods: Observational cross-sectional analysis of 154 men and women living with chronic HIV (66%men, mean age 47±7 years) and 69 HIV negative controls (59%men, age 46±7 years) with similar BMI and cardiovascular risk factors was performed. Serum I-FABP was measured by ELISA. Markers of inflammation and immune activation as well as lipopolysaccharides (LPS) were measured. Anthropometric measurements, DXA and single slice abdominal CT were obtained to assess body composition and visceral and subcutaneous adipose tissue areas. Results: Serum I-FABP was higher in the HIV-infected group (3373 pg/ml [1976-4527]) in comparison to the non-HIV control group (1633 pg/ml [1149- 2127]) (p<0.0001). Serum I-FABP was negatively associated with BMI (ρ=-0.36, p=<0.0001), truncal fat (ρ=-0.47, p<0.0001), arm fat (ρ=-0.48, p<0.0001), SAT (ρ=-0.24, p=0.003), and VAT (ρ=-0.28, p=0.0005), and positively associated with adiponectin (ρ=0.20, p=0.04) in the HIV-infected group. These relationships were not seen in the HIV-negative control group. Serum I-FABP was positively related to MCP-1 (ρ=0.19, p=0.005), CXCL10 (ρ=0.30, p=0.008), sCD163 (ρ=0.26, p=<0.0001), LPS (ρ=0.16, p=0.03) and to the percent of HLA- DR+CD38+ CD4+ T cells (ρ=0.26, p=0.02) among all participants. Conclusion: People living with chronic HIV have significantly higher I-FABP than HIV negative controls. I-FABP was also positively related to markers of microbial translocation, monocyte activation and T-cell activation markers. Interestingly, I-FABP was strongly negatively correlated with BMI and adiposity in subcutaneous and visceral fat compartments among people living with HIV, suggesting that intestinal damage from HIV infection may lead to impaired intestinal absorption and fat loss. Future studies to investigate the role of I-FABP or intestinal damage on fat metabolism are needed to elucidate mechanisms of this observed relationship in people living with HIV.

CROI 2018 274