CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Most participants (75%) identified as non-Hispanic Black, the average age was 49 years, 58% were post-menopausal, the median nadir CD4 cell count over the study period was 478, and 55% of participants were virally suppressed at all study visits. Repeated substance use ranged from 1.3% (cocaine use) to 66.1% (alcohol). Among all participants, 5.5% had LVSD. None of the repeated substance use measures were significantly associated with LVSD. Among participants without LVSD, 6.1% had LVDD. Adjusting for socioeconomic and clinical risk factors, the odds of LVDD were 5.22 times higher among women who reported repeated methamphetamine/amphetamine use (95% CI: 1.10, 24.73) and 1.87 times higher among those who reported repeated use of tobacco (95% CI: 1.10, 3.17). HIV-specific factors and other substances did not reach levels of significance . Conclusion: Repeated tobacco use and, to a much larger extent, repeated methamphetamine/amphetamine use had strong associations with LVDD in this population. Our findings highlight stimulant use as a potent risk factor for LVDD among WWH. Assessment and targeted interventions for WWH who use methamphetamine/amphetamine may lower cardiovascular risk in this population. Proteomic Signature of HIV-Associated Myocardial Fibrosis and Incident Heart Failure Tess E Peterson 1 , Virginia S. Hahn 1 , Ruin Moaddel 2 , Sabina Haberlen 3 , Frank Palella 4 , Michael Plankey 5 , Joao Lima 1 , Robert Gerszten 6 , Jerome Rotter 7 , Stephen Rich 8 , Damani Piggott 1 , Joseph B. Margolick 1 , Todd T. Brown 1 , Wendy S. Post 1 , Katherine C. Wu 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 National Institutes of Health, Bethesda, MD, USA, 3 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 Northwestern University, Chicago, IL, USA, 5 Georgetown University, Washington, DC, USA, 6 Beth Israel Deaconess Medical Center, Boston, MA, USA, 7 Los Angeles Biomedical Research Institute at Harbor– UCLA Medical Center, Torrance, CA, USA, 8 University of Virginia, Charlottesville, VA, USA Background: Persons living with HIV (PLWH) receiving antiretroviral therapy (ART) have greater myocardial fibrosis compared to persons without HIV (PWOH), which may contribute to risk of heart failure (HF). Mechanisms remain unclear but hypotheses include accentuated aging linked to chronic immune activation. We identified plasma proteomic signatures elevated among PLWH, cross-sectionally associated with myocardial fibrosis, and associated with incident HF among an external population of older PWOH. Methods: We performed proteomics (Olink) on plasma obtained concurrently with cardiac magnetic resonance imaging among PLWH and PWOH in Baltimore/DC and Chicago (SMASH). Myocardial fibrosis was measured by extracellular volume fraction (ECV). Proteins were assessed individually and as clusters defined using weighted gene co-expression network analysis. We estimated associations with HIV and elevated ECV (≥30% in women, ≥28% in men) using multivariable regression and explored protein relationships using annotated enrichment analysis. We tested associations of identified signatures with incident adjudicated HF using Cox regression among older PWOH (MESA). Results: Among 342 SMASH participants (age 55±6 years), 52% had elevated ECV and 61% were PLWH (88% on ART; 74% with undetectable plasma HIV RNA). Of 2594 proteins, 439 were associated with HIV seropositivity (SP) (414 excluding PLWH with detectable plasma HIV RNA) with a false discovery rate <0.05. We identified 39 (32) of these proteins as candidate contributors to the independent association between HIV SP and elevated ECV, including 9 proteins involved in apoptosis, 8 in cytokine signaling, 6 in T-cell activation, and 6 in the MAPK cascade. We identified one protein cluster associated with elevated ECV and HIV SP regardless of HIV viral suppression status, enriched in factors involved in TNF signaling, ephrin signaling, and extracellular matrix (ECM) organization. This protein cluster as well as 31 of 39 individual proteins were associated with incident HF among 2273 PWOH in MESA (age 68±9 years; 8.5 ±1.4 years of follow-up). Conclusion: Proteomic signatures that may in part reflect or contribute to HIV associated myocardial fibrosis are enriched in pathways of immune activation, cytokine signaling, and ECM organization, even among virally suppressed PLWH. These signatures also predict incident HF in a large independent cohort of older PWOH, suggesting underlying pathways that may portend risk of HF among PLWH may also drive HF pathogenesis among PWOH. The figure, table, or graphic for this abstract has been removed.

count or viral load) in terms of baseline characteristics, heart failure phenotypes by ejection fraction and presumed etiology, and outcomes after heart failure diagnosis including all-cause mortality (linked to national death statistics), and hospitalization for heart failure. Results: We included 14,829 individuals with HF, of whom 697 (4.7%) had HIV. Although 41% without HIV were female, only 19.7% with HIV were female with HIV, and the median age was 63 without HIV and 53 with HIV at time of HF diagnosis. Among those with HIV, the median nadir CD4 count was 133 (IQR 44, 275), and at HF diagnosis was 356 (IQR 173, 566). Persons with HIV had much higher proportions with documented alcohol, tobacco, opioid, cocaine and methamphetamine use (p<0.001 for each). 38% vs 33% had a reduced ejection fraction to <40% (p=0.009). There were no differences in the proportion with prior myocardial infarction or obstructive coronary artery disease on angiography. Median survival was 6.1 years (95% CI 5.4-7.1) among people with HIV compared to 11.3 years without HIV (95%CI 10.7-11.7). HIV was associated with higher risk of all-cause mortality (HR 1.55 95%CI 1.38-1.74; p<0.001; Figure) and lower odds of heart failure hospitalization (OR 0.51; 95%CI 0.39-0.66); p<0.001). Lower nadir CD4 and CD4 at the time of HF diagnosis were associated with worse survival: HR 1.37 for nadir < 200 (95%CI 1.08-1.75; p=0.009) and HR 1.69 for current <200 (95%CI 1.34-2.13; p<0.001), respectively. Viral load greater than 500 copies/ml was not associated with mortality (HR 1.02; 95%CI 0.80-1.31; p=0.87). Conclusion: Among people with HF who receive care within a municipal safety-net system, HIV infection is associated with diagnosis with HF ten years earlier and significantly elevated risk of mortality despite lower risk of HF hospitalization.

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Poster Abstracts

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Repeated Stimulant Use in the Context of Left Ventricular Dysfunction among Women Living with HIV Elise D Riley 1 , Yifei Ma 1 , Sanyog Shitole 1 , Katherine C. Wu 2 , Torsten Neilands 1 , Adam W. Carrico 3 , Claudia Martinez 4 , Denise Vidot 4 , Carlos Rodriguez 5 , Aruna Chandran 6 , Kathleen Weber 7 , Jason Lazar 8 , Antonina Foster 9 , Phyllis Tien 1 , Jorge R. Kizer 1 1 University of California San Francisco, San Francisco, CA, USA, 2 The Johns Hopkins Hospital, Baltimore, MD, USA, 3 Florida International University, Miami, FL, USA, 4 University of Miami, Miami, FL, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 The Johns Hopkins University, Baltimore, MD, USA, 7 Hektoen Institute of Medicine, Chicago, IL, USA, 8 State University of New York Downstate Medical Center Downstate Medical Center, Brooklyn, NY, USA, 9 Emory University, Atlanta, GA, USA Background: HIV is associated with an increased risk of heart failure (HF), which is especially pronounced in women. This is concerning because women with HIV (WWH) come predominantly from vulnerable race-ethnic minority groups that are themselves at high risk for HF. In addition, people with HIV have a disproportionately high prevalence of substance use, which is also associated with heart disease. The extent to which specific substances or substance types relate to precursors of clinical HF, such as left ventricular systolic dysfunction (LVDD) and diastolic dysfunction (LVDD), in WWH remains under-studied. Methods: We investigated cross-sectional associations between repeated use of various substances and pre-HF phenotypes, LVSD and LVDD, in the Women's Interagency HIV Study. We defined exposures as self-reported substance use (i.e., tobacco, alcohol, cannabis, cocaine, methamphetamine/amphetamine, opioids, and sedatives) at ≥2 study visits ("repeated use") compared to no use or single-visit use. Standardized echocardiograms were performed from 2014 to 2019 in 1,162 WWH. LVSD and LVDD were defined by American Society of Echocardiography criteria.

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