WASHINGTON STATE CONVENTION CENTER

February 13–16, 2017

Conference Dates and Location: 
February 13–16, 2017 | Seattle, Washington
Abstract Number: 
126

IL-1β INHIBITION SIGNIFICANTLY REDUCES ATHEROSCLEROTIC INFLAMMATION IN TREATED HIV

Author(s): 

Priscilla Hsue1, Steven G. Deeks1, Amorina E. Ishai2, Sophia Hur1, Danny Li1, Felicia Sterman3, Jay Lalezari4, Adam Rupert5, Peter Ganz1, Ahmed Tawakol2

1Univ of California San Francisco, San Francisco, CA, USA,2Massachusetts General Hosp, Boston, MA, USA,3California Pacific Med Cntr, San Francisco, CA, USA,4Quest Clinical Rsr, San Francisco, CA, USA,5Natl Inst of Hlth, Frederick, MD, USA

Abstract Body: 

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 upstream mediator 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.

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.

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 marrow metabolic activity (BM TBR: 3.78±0.72 vs. 3.37±0.55, p<0.001, Figure 1B).

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 marrow metabolic 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.

Session Number: 
O-12
Session Title: 
INFLAMMATION AND AGE-RELATED COMPLICATIONS
Presenting Author: 
Priscilla Hsue
Presenter Institution: 
University of California, San Francisco