HIV-Associated Proteomic Signature of Myocardial Fibrosis and Incident Heart Failure

Abstract Background People with 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 Participants were age 55±6 years, 25% female, 61% PWH (88% on antiretroviral therapy, 74% undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and one cluster of 42 proteins that were higher among PWH vs. PWOH and positively associated with elevated ECV, independent of risk factors (FDR0.05). Among an independent cohort of 3223 PWOH (age 68±9 years; 52% female; 118 incident HF cases over 9.8±1.4 years), we found this protein cluster and 34 of 39 individual proteins were associated with time to incident HF. This signature was statistically enriched for T cell activation, TNF signaling, ephrin signaling, and tissue maintenance and repair. Conclusion We identified an HIV-related proteomic signature associated with myocardial fibrosis regardless of HIV serostatus and that predicted incident HF among the general population. Our results identify several novel associations related to specific immune processes that may contribute to risk of myocardial fibrosis and subsequent HF among both PWH and PWOH.