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Although rollout of combined antiretroviral treatment (cART) has blunted human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) onset, there is increased development of cardiovascular diseases (CVDs) in HIV-infected individuals. While most HIV-infected individuals on cART achieve viral suppression, this may not necessarily result in complete immunological recovery. This study therefore evaluated T-cell-mediated changes and coagulation markers in HIV-positive individuals to ascertain their potential to increase CVD risk. Eighty participants were recruited (Worcester, South Africa), and fasted blood was collected to evaluate: 1) immune activation (CD38 expression on CD4+and CD8+T cells) and thrombus formation [tissue factor (CD142)] on CD4+and CD8+T cells; 2) monocyte subpopulations (nonclassical, intermediate, and classical); and 3) classical regulatory T (Treg) cells with activation markers [glycoprotein A repetitions predominant (GARP) and special AT-rich sequence-binding protein 1 (SATB-1)]. High- and low-density lipoprotein subclasses (Lipoprint) were also determined. This study revealed four key findings for HIV-positive patients: 1) coexpression of the CD142 coagulation marker together with immune activation on both CD4+and CD8+T cells during chronic infection stages; 2) Treg cell activation and upregulated GARP and SATB-1 contributing to Treg dysfunction in chronic HIV; 3) proatherogenic monocyte subset expansion with significant correlation between T-cell activation and macrophage activation (marker: CD163); and 4) significant correlation between immune activation and lipid subclasses, revealing crucial changes that can be missed by traditional lipid marker assessments (LDL and HDL). These data also implicate lipopolysaccharide-binding protein as a crucial link between immune activation, lipid alterations, and increased CVD risk.NEW & NOTEWORTHY With combined antiretroviral treatment rollout, HIV-AIDS patients are increasingly associated with cardiovascular diseases onset. This study demonstrated the significant interplay between adaptive immune cell activation and monocyte/macrophage markers in especially HIV-positive individuals with virological failure and on second line treatment. Our data also show a unique link between immune activation and lipid subclass alterations, revealing important changes that can be missed by traditional lipid marker assessments (e.g., LDL and HDL).

Aims Although there is evidence linking sugar-sweetened beverage (SSB) intake with the development of cardio-metabolic diseases, the underlying mechanisms remain unclear. The current study therefore evaluated the effects of SSB consumption by establishing a unique in-house in vivo experimental model. Main methods Male Wistar rats were divided into two groups: a) one consuming a popular local SSB (SSB- Jive), and b) a control group (Control-water) for a period of three and six months (n = 6 per group), respectively. Rats were gavaged on a daily basis with an experimental dosage amounting to half a glass per day (in human terms) (SSB vs. water). Cardiac function was assessed at baseline (echocardiography) and following ex vivo ischemia-reperfusion of the isolated perfused working rat heart. Oral glucose tolerance tests and mitochondrial respiratory analyses were also performed. In addition, the role of non-oxidative glucose pathways (NOGPs), i.e. the polyol pathway, hexosamine biosynthetic pathway (HBP) and PKC were assessed. Key findings These data show that SSB intake: a) resulted in increased weight gain, but did not elicit major effects in terms of insulin resistance and cardiac function after three and six months, respectively; b) triggered myocardial NOGP activation after three months with a reversion after six months; and c) resulted in some impairment in mitochondrial respiratory capacity in response to fatty acid substrate supply after six months. Significance SSB intake did not result in cardiac dysfunction or insulin resistance. However, early changes at the molecular level may increase risk in the longer term.

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.