CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

126 IL-1Β INHIBITION SIGNIFICANTLY REDUCES ATHEROSCLEROTIC INFLAMMATION IN TREATED HIV Priscilla Hsue 1 , Steven G. Deeks 1 , Amorina E. Ishai 2 , Sophia Hur 1 , Danny Li 1 , Felicia Sterman 3 , Jay Lalezari 4 , Adam Rupert 5 , Peter Ganz 1 , Ahmed Tawakol 2 1 Univ of California San Francisco, San Francisco, CA, USA, 2 Massachusetts General Hosp, Boston, MA, USA, 3 California Pacific Med Cntr, San Francisco, CA, USA, 4 Quest Clinical Rsr, San Francisco, CA, USA, 5 Natl Inst of Hlth, Frederick, MD, USA Background: HIV infection is associated with an increased burden of atherothrombotic events, likely as a result of increased atherosclerotic inflammation. The IL-1 pathway is an upstreammediator of inflammation and inducer of innate immunity. IL-1β binds to the IL-1 receptor and is linked to both stimulating atherogenesis and HIV disease pathogenesis. The purpose of this pilot study was to evaluate the impact of IL-1β inhibition on inflammatory markers and atherosclerotic plaque inflammation using fluorodeoxyglucose positron emission tomography imaging (FDG-PET) in HIV. Methods: Adults with treated and suppressed HIV infection and 1 cardiovascular risk factor (n= 10) were treated with a monoclonal antibody to IL-1β (canakinumab [CKB],

150mg subcutaneous injection administered once). FDG-PET imaging was performed before and 8 weeks after treatment to measure atherosclerotic inflammation in the aorta and carotids. Arterial wall FDG uptake (target) was normalized to blood pool (background), yielding a target to background ratio (TBR). The most diseased segment (MDS) was defined as the 1.5 cm segment with the highest TBR at baseline. All analyses were performed while blinded to time point. Results: The median age was 59 (IQR 55 to 65), all were male, and 80%were on statin therapy. The median CD4 count was 748 (IQR 570 to 1142) and all had undetectable HIV RNA levels. CKB was well tolerated without a significant change in CD4 count or HIV RNA level. At 8 weeks, CKB reduced hsCRP (median [IQR]: 0.87 [0.56, 4.17] vs. 0.64 [0.24, 2.44] mg/mL, baseline vs. follow- up, p=0.02), and IL-6 (1.10 [0.69, 1.33] vs. 0.70 [0.48, 1.06] pg/ml, p=0.005). CKB attenuated arterial inflammation by 10% (mean index MD±SSD: 3.29±0.57 vs. 2.98±0.64, p=0.046, Figure 1A). This was accompanied by an 11% reduction in bone marrowmetabolic activity (BM TBR: 3.78±0.72 vs. 3.37±0.55, p<0.001, Figure 1B).

Oral Abstracts

Conclusion: In this first study to examine the effect of a potent anti-inflammatory strategy on atherosclerotic inflammation in HIV, we observed a substantial reduction in atherosclerotic inflammation, bone marrowmetabolic activity, and inflammatory markers (hsCRP and IL-6). Larger, placebo-controlled studies are under way to further evaluate the impact of IL-1β inhibition on atherosclerotic inflammation in this population, and to assess whether this approach will translate into reductions in atherothrombotic events. 127 HYPERBILIRUBINEMIA PREVENTS CARDIOVASCULAR DISEASE FOR HIV+ AND HIV- INDIVIDUALS Vincent C. Marconi 1 , Kaku So-Armah 2 , Janet Tate 3 , Joseph Lim 4 , Vincent Lo Re 5 , Adeel A. Butt 6 , Matthew B. Goetz 7 , Maria Rodriguez-Barradas 8 , Amy Justice 3 , Matthew Freiberg 9 1 Emory Univ, Atlanta, GA, USA, 2 Boston Univ, Boston, MA, USA, 3 VA Connecticut Hlthcare System, West Haven, CT, USA, 4 Yale Univ, New Haven, CT, USA, 5 Univ of Pennsylvania, Philadelphia, PA, USA, 6 Weill Cornell Med Coll, New York, NY, USA, 7 VA Greater Los Angeles Hlth Care System, Los Angeles, CA, USA, 8 Baylor Coll of Med, Houston, TX, USA, 9 Vanderbilt Univ, Nashville, TN, USA Background: Hyperbilirubinemia may protect against cardiovascular disease (CVD) by reducing oxidative stress and via its anti-atherogenic properties. Whether elevated bilirubin reduces risk of CVD events including among HIV positive (HIV+) people independently of atazanavir (ATV) use is unclear. ATV can cause unconjugated hyperbilirubinemia by competitive inhibition of the uridine diphosphate-glucuronosyl transferase (UGT) 1A1 enzyme. We assessed whether elevated bilirubin independently reduced the risk of heart failure (HF) and acute myocardial infarction (AMI) among participants in the Veterans Aging Cohort Study (VACS). Methods: VACS participants, without CVD at baseline (first clinical visit after 4/1/2003) were included. The total bilirubin from clinical labs closest to baseline was categorized into quartiles. HF and AMI were assessed using VA, VA Fee For Service and Medicare ICD-9 codes. Participants were followed until first HF or AMI, death, last VA encounter or 12/31/2011. Cox regression was used to estimate HF/AMI risk adjusting for baseline confounders including HIV and hepatitis C, demographics, Framingham CVD risk factors, and substance abuse/dependence. Analyses restricted to HIV+ participants were further adjusted for HIV viremia and ATV use. Results: There were 96,373 participants; mean age was 49 years, 48%were African American, and 97%were men. There were 3,844 incident HF events (median follow up 6.9 years) and 1,932 incident AMI events over (median follow up 7.4 years). Among the HIV+ participants with bilirubin >75th percentile (≥0.9 mg/dL), 9%were on ATV compared to 3%, with bilirubin <25th percentile (<0.04 mg/dL). In unadjusted models, bilirubin was inversely associated with HF and AMI risk. After adjusting for CVD risk factors, higher bilirubin was associated with a lower hazard ratio (HR) for HF and AMI (Table). When the same model included only HIV+ participants (N=30,425), results persisted for HF and similar but non-significant associations were observed for AMI. Death rates were highest in the lowest and highest bilirubin quartiles. Conclusion: VACS participants with elevated bilirubin had lower risk of incident HF and AMI events after adjusting for known risk factors. This association persisted for HF among HIV+ people but was attenuated for AMI. Future studies, should investigate how this apparently protective effect of elevated bilirubin may be harnessed to reduce CVD risk or improve CVD risk estimation among HIV+ people.

128LB ASSOCIATION BETWEEN CARDIOVASCULAR DISEASE & CONTEMPORARILY USED PROTEASE INHIBITORS Lene Ryom 1 , Jens D. Lundgren 2 , Wafaa M. El-Sadr 3 , Peter Reiss 4 , Andrew Phillips 5 , Ole Kirk 6 , Rainer Weber 7 , Caroline Sabin 5 , Amanda Mocroft 8 , for the D:A:D Study Group 1 CHIP, Copenhagen, Denmark, 2 Univ of Copenhagen, Copenhagen, Denmark, 3 ICAP at Columbia Univ, New York, NY, USA, 4 Stichting HIV Monitoring and Academic Med Cntr Amsterdam, Amsterdam, Netherlands, 5 Univ Coll London, London, UK, 6 Rigshosp, Copenhagen, Denmark, 7 Univ of Zurich, Zurich, Switzerland, 8 Univ Coll London, London, UK Background: While the use of older protease inhibitors (PIs) including indinavir (incidence rate ratio (IRR) 1.47/5 years) and lopinavir boosted with ritonavir (/r) (IRR 1.54/5 years) has been associated with excess risk of cardiovascular disease (CVD) it is unknown whether this also applies to contemporarily used PIs.

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CROI 2017