HIV-Mediated Immunometabolic Perturbations and Links to Cardiovascular Disease Risk

Background: Although roll-out of combined anti-retroviral treatment (cART) has blunted HIV-AIDS onset, studies show increased development of cardiovascular diseases (CVD) in HIV-infected individuals. This study aimed to identify changes in immune cells (T cells, monocyte subsets) and determine their relationship to: (a) classical markers of HIV progression (CD4 count, viral load), (b) immune activation status and coagulation, and (c) traditional lipid profile/subclasses. Methods: Eighty participants were recruited (Worcester, South Africa) and fasted blood collected to evaluate: a) traditional lipid profile, b) immune markers, c) monocyte subpopulations (non-classical, intermediate, classical) by flow cytometry together with tissue factor (marker: thrombus formation) and CD38 (marker:immune activation) expression on CD4 and CD8 T cells. Classical regulatory T cells (Treg) with activation markers (glycoprotein A repetitions predominant [GARP], special AT-rich sequence-binding protein 1) were assessed together with high-and low-density lipoprotein subclasses (Lipoprint). Findings: This study revealed four key findings in HIV-positive patients: a) co-expression of a coagulation marker (tissue factor) together with immune activation on CD4 and CD8 T cells (irrespective of cART), b) Treg cell activation and upregulated GARP contributing to persistent  immune activation, c) Pro-atherogenic monocyte subset expansion; and d) Lipopolysaccharide binding protein (LBP) as a key modulator mediating immunometabolic perturbations. Interpretation: These findings alert to the future clinical management of HIV-positive patients and highlight the need for earlier therapeutic interventions to address chronic inflammation, immune activation and LBP-mediated lipid subclass effects. This strategy should decrease coagulation and lower CVD risk. Funding Statement: This work was supported by the Medical Research Council and Stellenbosch University [MFE]. Declaration of Interests: None declared. Ethics Approval Statement: This study complies with the Declaration of Helsinki and ethical approval was obtained from the Human Research Ethics Committee of Stellenbosch University and the Department of Health (Western Cape Government, South Africa). Prior to the study, all participants were informed about procedures and consent forms were signed by all.