Although the extensive rollout of antiretroviral (ARV) therapy resulted in a longer life expectancy for people living with human immunodeficiency virus (PLHIV), such individuals display a relatively increased occurrence of cardiovascular diseases (CVD). This health challenge stimulated significant research interests in the field, leading to an improved understanding of both lifestyle-related risk factors and the underlying mechanisms of CVD onset in PLHIV. However, despite such progress, the precise role of various risk factors and mechanisms underlying the development of HIV-mediated CVD still remains relatively poorly understood. Therefore, we review CVD onset in PLHIV and focus on 1) the spectrum of cardiovascular complications that typically manifest in such persons and 2) underlying mechanisms that are implicated in this process. Here, the contributions of such factors and modulators and underlying mechanisms are considered in a holistic and integrative manner to generate a unifying hypothesis that includes identification of the core pathways mediating CVD onset. The review focuses on the sub-Saharan African context, as there are relatively high numbers of PLHIV residing within this region, indicating that the greater CVD risk will increasingly threaten the well-being and health of its citizens. It is our opinion that such an approach helps point the way for future research efforts to improve treatment strategies and/or lifestyle-related modifications for PLHIV.

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).

Although the underlying mechanisms driving human immunodeficiency virus (HIV)-mediated cardiovascular diseases (CVD) onset and progression remain unclear, the role of chronic immune activation as a significant mediator is increasingly being highlighted. Chronic inflammation is a characteristic feature of CVD and considered a contributor to diastolic dysfunction, heart failure, and sudden cardiac death. This can trigger downstream effects that result in the increased release of pro-coagulant, pro-fibrotic, and pro-inflammatory cytokines. Subsequently, this can lead to an enhanced thrombotic state (by platelet activation), endothelial dysfunction, and myocardial fibrosis. Of note, recent studies have revealed that myocardial fibrosis is emerging as a mediator of HIV-related CVD. Together, such factors can eventually result in systolic and diastolic dysfunction, and an increased risk for CVD. In light of this, the current review article will focus on (a) the contributions of a chronic inflammatory state and persistent immune activation, and (b) the role of immune cells (mainly platelets) and cardiac fibrosis in terms of HIV-related CVD onset/progression. It is our opinion that such a focus may lead to the development of promising therapeutic targets for the treatment and management of CVD in HIV-positive patients.

No abstract