Human Immunodeficiency Virus–Associated Proteomic Signature of Myocardial Fibrosis and Incident Heart Failure

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) are at higher risk of myocardial fibrosis and subsequent heart failure (HF) compared to people without HIV (PWOH). Mechanisms underlying this risk and its specificity to PWH are unclear. METHODS: We measured 2594 proteins in plasma obtained concurrently with cardiovascular magnetic resonance imaging among 342 PWH and PWOH. We estimated associations with HIV serostatus and myocardial fibrosis (elevated extracellular volume fraction [ECV] ≥30% among women, ≥28% among men) using multivariable regression. Among an independent community-based cohort, we estimated associations between the identified signature and time to incident HF. RESULTS: Mean age of participants was 55 (standard deviation [SD], 6) years, 25% were female, 61% were PWH (88% on antiretroviral therapy, 74% with undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and 1 cluster of 42 proteins that were higher among PWH versus PWOH and positively associated with elevated ECV, independent of risk factors (false discovery rate