CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

700 CT FAT DENSITY REFLECTS HISTOLOGIC FAT QUALITY IN ART-TREATED, HIV-1-INFECTED ADULTS Jordan E. Lake 1 , Carlee Moser 2 , Liz Johnston 2 , Clara Magyar 3 , Scott D. Nelson 3 , Kristine Erlandson 4 , Todd Brown 5 , Grace A. McComsey 6 1 Univ of Texas, Houston, TX, USA, 2 Harvard Univ, Boston, MA, USA, 3 Univ of California Los Angeles, Los Angeles, CA, 4 Univ of Colorado, Aurora, CO, USA, 5 The Johns Hopkins Univ, Baltimore, MD, USA, 6 Case Western Reserve Univ, Cleveland, OH, USA Background: Adipose tissue (AT) quality and quantity may independently determine metabolic health. The gold standard for determining AT quality is measurement of adipocyte size on microscopic examination of biopsy specimens. Computed tomography (CT)-quantified AT density is believed to reflect adipocyte quality (lower density=larger, less differentiated, poor quality adipocytes); however, little human data exists to support this hypothesis. Using subcutaneous abdominal AT (SAT) biopsy specimens and L4-L5 single slice CT scans from a completed trial of antiretroviral therapy (ART) initiation, we previously demonstrated CT’s ability to reflect biopsy-confirmed AT quality in treatment-naïve, HIV-1-infected adults. Significant changes in fat quality and quantity may occur on ART. As such, we explored whether CT density accurately reflects AT quality in ART-treated individuals. Methods: AIDS Clinical Trials Group study A5224s participants were included in the analysis if they remained on their original ART regimen (ABC/3TC or TDF/FTC with either EFV or RTV/ATV) and had HIV-1 RNA <50 copies/mL, subcutaneous abdominal SAT biopsy and/or CT SAT or visceral AT (VAT) data at 96 weeks. Associations between SAT density (in Hounsfield Units, HU) and mean adipocyte area (in μm2) were assessed using Spearman’s correlations, and linear regression models adjusted for clinical and demographic characteristics. Correlations between SAT and VAT density were also determined. Results: Participants (n=30) were 89%were male and 67%white non-Hispanic. Median age was 41 years, body mass index 26.0 kg/m2 and CD4+ T lymphocyte count 219 cells/ mm3. After 96 weeks of ART, median SAT density was -104 HU, VAT density -90 HU and adipocyte area 2759 μm2. Mean adipocyte area correlated with SAT density (r=-0.57, p=0.003), with some variation by ART regimen (Table). This relationship persisted in models adjusting for age, race, sex, CD4+ T lymphocyte count and SAT area. SAT and VAT density also correlated with each other (r=0.55, p=0.002). Conclusion: CT SAT density correlates with biopsy-quantified subcutaneous adipocyte size and with VAT density in ART-treated, HIV-1 infected adults. CT may be a useful tool for non-invasive assessment of AT quality in both the SAT and VAT depots, although additional studies are needed to assess ART effects and relationships between CT density and clinical measures of AT function. 701 ASSOCIATION OF NAFLD WITH ADIPOKINE AND INFLAMMATORY MARKERS DIFFERS BY HIV STATUS Jennifer Price 1 , Ruibin Wang 2 , Eric Seaberg 2 , Matthew Budoff 3 , Lawrence Kingsley 4 , Frank J. Palella 5 , Mallory Witt 6 , Wendy Post 2 , Chloe Thio 2 1 Univ California San Francisco, San Francisco, CA, USA, 2 The Johns Hopkins Univ, Baltimore, MD, USA, 3 Harbor–UCLA Med Cntr, Torrance, CA, USA, 4 Univ of Pittsburgh, Pittsburgh, PA, USA, 5 Northwestern Univ, Chicago, IL, USA, 6 Los Angeles Biomed Rsr Inst at Harbor–UCLA Med Cntr, Torrance, CA, USA Background: Adipokines and serummarkers of immune activation are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in HIV-infected (HIV+) persons. We evaluated associations between NAFLD and these markers in HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study (MACS). Methods: Non-contrast CT was used to assess fatty liver (liver/spleen Hounsfield units<1) and to measure abdominal visceral adipose tissue (VAT) volume in 552 MACS participants who drank <3 alcoholic drinks/day and who were not infected with hepatitis C or B viruses. We measured adipokine and inflammatory/immune activation marker levels at the time of CT. Multivariable logistic regression was used to assess associations of biomarkers and VAT with NAFLD and to evaluate potential interactions between HIV serostatus and biomarkers. Results: The 348 HIV+men (89% on HAART and 82%with undetectable HIV RNA) had significantly higher levels of sCD163, CRP, ICAM-I, and TNFαR2 and significantly lower levels of adiponectin and leptin than the 204 HIV- men. The 84 men (15%) with NAFLD (47 HIV+, 37 HIV-) were more likely to be non-Hispanic white, had higher median BMI, VAT, abdominal subcutaneous tissue, HOMA-IR, and triglyceride levels and had lower HDL levels than men without NAFLD. Among the HIV- men, in fully-adjusted models including VAT, we found a higher odds of NAFLD with increasing ICAM-1 (OR 4.81, p=0.004), CRP (OR 1.41, p=0.015), and TNFαR2 (OR 5.48, p=0.004) (Table). In contrast, among the HIV+men, only higher adiponectin was independently protective against NAFLD in fully-adjusted models (OR 0.68, p=0.033). Moreover, we found a significant negative interaction between HIV serostatus and CRP (p=0.045) and TNFαR2 levels (p=0.005), indicating that these cytokines were associated with NAFLD only among HIV- men (see Table). In an analysis restricted to the HIV+, adjustment for HIV-related factors, including current and nadir CD4, HIV RNA, and current and cumulative HAART did not alter our findings. Conclusion: Higher pro-inflammatory cytokine levels (ICAM-1, CRP and TNFαR2) were independently associated with NAFLD among HIV- men but not among HIV+men, in whom lower levels of adiponectin (which is anti-inflammatory) were. These findings may indicate that among HIV+ persons, diminished levels of anti-inflammatory markers may be important in the pathogenesis of NAFLD than a higher inflammatory state.

Poster and Themed Discussion Abstracts

702

PREVALENCE AND RISK FACTORS FOR HEPATIC STEATOSIS IN HIV+ PERSONS Jessie Torgersen 1 , Kaku So-Armah 2 , Matthew Freiberg 3 , Matthew Budoff 4 , Joseph Lim 5 , Adeel Butt 6 , Maria Rodriguez-Barradas 7 , Amy Justice 8 , Jay Kostman 9 , Vincent Lo Re 1

CROI 2017 307