Obesity Is Associated With Higher Levels of Circulating Cytokines Involved in the Development of Cardiovascular Disease in People Living With HIV
Authors: Savinelli Stefano , McGettrick Pádraig , Garcia Leon Alejandro A. , Tinago Willard , Haran Emma , Barco Elena Alvarez , Landay Alan L. , Mallon Patrick W. G. , Feeney Eoin R. ,   On behalf of the All Ireland Infectious Diseases Cohort Study
Published: August 2024

Background:

Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterized. We aimed to analyze the difference in circulating cytokines involved in pathways associated with comorbidities in PLWH according to the presence or absence of obesity.

Methods:

Age- and sex-matched PLWH with and without obesity (body mass index ≥30 kg/m2) from a multicenter, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (high sensitivity C-Reactive Protein [hsCRP], interleukin (IL)-2, IL-6, tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, tumor necrosis factor-alpha, interferon-gamma, IL-18), coagulation (von Willebrand Factor [vWF], D-dimer, soluble CD40 ligand), endothelial function (E-selectin, P-selectin, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1), atherosclerosis (myeloperoxidase [MPO], lipoprotein-associated phospholipase A2), immune regulation (IL-1 receptor antagonist [IL-1RA]), innate immune activation (macrophage inflammatory protein-1, monocyte chemoattractant protein-1, soluble CD163, soluble CD14), and microbial translocation (lipopolysaccharide binding protein) were measured in the 2 groups. Between-group difference in biomarkers were assessed using Mann–Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, sex, ethnicity, smoking status, and antiretroviral therapy.

Results:

Ninety-nine antiretroviral therapy–treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and lipopolysaccharide binding protein. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation, and atherosclerosis pathways, were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (adjusted odds ratio 2.7, 95% CI: [1.7 to 4.29]), IL-6 (3.77 [1.43–9.93]), vWF (5.33 [1.51–18.75]), E-selectin (6.28 [1.36–29.04]), MPO (6.85 [1.87–25.04]), and IL-1RA (6.45 [2.28–18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation.

Conclusions:

Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis, and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point toward an unfavorable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.