Am Heart J. 2026 Feb 28:107400. doi: 10.1016/j.ahj.2026.107400. Online ahead of print.
ABSTRACT
RATIONALE: People with HIV (PWH) are at increased risk of cardiovascular disease. Moderate lipid lowering with statins has been demonstrated to reduce cardiovascular risk among PWH. Accordingly, evaluation of more potent lipid lowering strategies for prevention are needed, especially for PWH at higher risk. Prior research suggests that proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors safely lower low density lipoprotein cholesterol by 60% among people with HIV, but the impact of PCSK9 inhibitors on arterial inflammation, endothelial function, coronary plaque, or markers of immune dysfunction among PWH remains unknown.
METHODS: The Effect of PCSK9 Inhibition on Cardiovascular Risk in Treated HIV Infection (EPIC-HIV) Study is a randomized, placebo-controlled, double-blinded clinical trial. Adults at least 40 years old with treated and virally suppressed HIV and at least one cardiovascular risk factor (primary prevention) or a prior cardiovascular event (secondary prevention) are randomized in a 2:1 ratio to alirocumab or matching placebo injected subcutaneously. 18F-FDG PET/CT, coronary computed tomographic angiography (CCTA), and flow-mediated dilation of the brachial artery are conducted at baseline and after one year of treatment. The primary study outcome is change in arterial inflammation assessed using the target-to-background ratio of the most diseased arterial segment on PET/CT from baseline to 1 year, and key secondary endpoints will include change in noncalcified coronary plaque on CCTA, change in endothelial function, and safety according to the intention-to-treat principle.
ENROLLMENT: 118 participants were randomized. Mean age was 59.5 years and 6% were female.
CONCLUSIONS: The EPIC-HIV Study will provide evidence regarding the mechanisms by which potent lipid lowering with PCSK9 inhibitors may alter the pathogenesis of atherosclerosis among PWH.
ETHICS, FUNDING DISSEMINATION: This investigator-initiated study was funded by the National Heart, Lung, and Blood Institute (R61/R33 HL141047). Study drug and placebo were provided by the manufacturer. The work of IS was supported by the intramural research program of NIH. The contributions of the NIH authors are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. The study protocol was approved by the Institutional Review Board at the University of California San Francisco. Written informed consent was obtained from all study participants. The funders will have no role in the decision to submit the manuscript for publication in a peer-reviewed journal.
TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT03207945.
PMID:41771366 | DOI:10.1016/j.ahj.2026.107400