Project Summary
Persons living with HIV infection (PLWH) have a 2-fold 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 remains poorly understood, studies demonstrate that atherosclerosis in
the setting of HIV is distinct and characterized by heightened arterial inflammation as assessed by FDG-
PET/CT. HIV and antiretroviral medication can worsen cardiometabolic parameters. Thus a therapeutic
strategy that can lower lipids, inflammation, and improve glycemic parameters may be even more
advantageous in HIV. Bempedoic acid (BA, an inhibitor of ATP citrate lyase), is safely tolerated, significantly
lowers LDL-C and inflammatory markers (on top of statin therapy), and is FDA approved for individuals with
heterozygous familial hypercholesterolemia or with established ASCVD who require additional LDL-C lowering.
Additionally, BA has a protective effect on glycemic parameters and may reduce adiposity. Given the key role
of lipids and inflammation in atherosclerosis in HIV, the purpose of this proof-of-concept mechanistic trial is to
evaluate the impact of BA on the biology of HIV-associated atherosclerosis. We will perform a randomized
placebo controlled study of effectively treated PLWH aged 40 years and older with either known CVD or 1 CVD
risk factor to study the effect of BA on arterial inflammation (assessed by FDG-PET/CT), lipid levels,
biomarkers of inflammatory/immune activation, cardiometabolic indices, and non-calcified plaque in the
coronary arteries (assessed by CCTA). This multicenter trial will include PLWH enrolled at UCSF, UCLA, and
Univ. of Utah. Long term collaborators at MGH will serve as the core facility for the imaging end-points. We
have 3 specific aims for the: Cholesterol and inflammation Lowering via BEmpedoic Acid, an ACL-inhibiting
Regimen in HIV Trial (CLEAR HIV Trial): Aim 1: To determine whether BA can safely reduce arterial
inflammation including carotid plaque as assessed by FDG-PET/CT; Aim 2: To determine whether BA
improves cardiometabolic measures (lipid, inflammatory, glycemic and adipose parameters) among PLWH.
Exploratory objectives will be to assess BA’s effect (vs. placebo) on glycemic as well as adipose tissue
measures (HbA1c, HOMA IR, and adipose tissue volumes); Aim 3: To evaluate the impact of BA on non-
calcified coronary plaque volume as measured by coronary CT angiography (CCTA) and to determine whether
changes in arterial inflammation are correlated with reduction in coronary plaques. This application combines
(1) a successful multidisciplinary team with a strong record of collaboration and expertise in studying
interventions in HIV, (2) the ability to rapidly recruit subjects from existing HIV-infected cohorts, (3) leveraging
of resources including study drug/placebo. Identifying novel therapies to reduce CV risk are essential to
improve mortality among PLWH, and results from this study will form the groundwork for a future trial to
evaluate the impact of additional reduction of LDL-C and inflammation using BA on clinical events in HIV.