NIH grant: Evaluation of Glucagon-Like Peptide-1 Receptor Agonist on Pathophysiology of Inflammation and Atherosclerosis in Persons Living With HIV: A Multicenter Randomized Placebo-Controlled Tri (1R01HL184987-01)

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NIH grant 1R01HL184987-01: Evaluation of Glucagon-Like Peptide-1 Receptor Agonist on Pathophysiology of Inflammation and Atherosclerosis in Persons Living With HIV: A Multicenter Randomized Placebo-Controlled Tri
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Priscilla Y. Hsue. Award: $1282827.
Start: 2026-07-10T00:00:00.
Project Summary
People living with HIV (PWH) have a higher risk of myocardial infarction and are twice as likely to develop
cardiovascular disease accounting for a significant global burden of disease. While the mechanism
underlying this excess risk is multifactorial, studies demonstrate that atherosclerosis in the setting of HIV is
distinct and characterized by heightened arterial inflammation. Glucagon-like peptide-1 receptor agonist
(GLP1-RA) using semaglutide is associated with reductions in major adverse cardiovascular events along
with improvements in blood pressure, weight, and inflammatory markers in the general population with or
without diabetes. While the precise mechanism by which GLP1-RA improves cardiovascular events remains
unknown, GLP1-RA lowers production of inflammatory cytokines including IL-6, IL-1B, TNF-alpha and CRP
as well as reduces macrophage infiltration in blood vessels and tissues. Among PWH, our team showed
that semaglutide was safely tolerated and improved cardiometabolic indices and liver disease; however, the
impact of this approach on atherosclerosis in HIV has not been evaluated. Given the key role of monocytes/
macrophages and inflammation in HIV- associated cardiovascular disease (CVD), the purpose of this proof-
of-concept mechanistic trial is to evaluate the impact of GLP1-RA using semaglutide on the biology of HIV-
associated atherosclerosis. We will perform a randomized placebo-controlled study of 125 treated and
suppressed PWH aged 40 years and older with either known CVD or 1 risk factor for CVD to study the effect
of GLP1-RA using oral semaglutide at 7mg once daily on arterial inflammation (assessed by FDG-PET/CT),
biomarkers of inflammatory/immune activation, non-calcified plaque, and coronary inflammation in the
coronary arteries (assessed by coronary computed tomography angiography, CCTA). This multicenter trial
will include PWH enrolled at UCLA, UTHealth Houston, and Mass General Brigham
(MGB) which are all sites with extensive experience in performing trials among PWH. Long time
collaborators at MGB will serve as the core facility for the imaging endpoints. We have 3 specific aims for
the Evaluation Of Glucagon-Like Peptide-1 Receptor Agonist on PathophysiologY of InflaMmation and
Atherosclerosis in Persons Living With HIV: A Multicenter Randomized Placebo-Controlled Trial (Olympic-
HIV Trial): Aim 1: To determine whether GLP1-RA using semaglutide can reduce arterial inflammation as
assessed by FDG-PET/CT. We will also assess the impact of GLP1-RA on hematopoietic tissues; Aim 2: To
determine the effect of GLP1-RA using semaglutide on markers of inflammation/immune activation and
cardiometabolic indices (weight, adipose tissue measurements, lipids and HOMA-IR); Aim 3: To explore the
impact of GLP1-RA on non-calcified coronary plaque (NCP) volume as measured by CCTA and coronary
inflammation using pericoronary adipose tissue density(PCAT). These results will provide much needed data
for the purpose of informing a larger clinical outcomes study in PWH.

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