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The prevalence of cardiovascular death in the HIV-infected population is higher than in uninfected individuals. Growing evidence suggests that HIV infection itself is directly linked to endothelial activation and dysfunction. Therefore, the aim of this study was to investigate whether endothelial activation is present in African subjects with HIV infection and identify its possible determinants. Eighty HIV-infected treatment-naive cases, categorized into two groups based on CD4 count (38 subjects with CD4 count ≤350 cells/mm 3 and 42 subjects with CD4 count >350 cells/mm 3 ), were compared with 60 HIV-uninfected controls. A small subgroup of the HIV-infected participants ( n  = 13) were followed up for 18 months following initiation of antiretroviral therapy (ART). Anthropometric data, fasting lipid and glucose levels, viral load, and CD4 counts were measured as were serum levels of intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1, von Willebrand factor (vWF), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). The HIV-infected low CD4 group had higher levels of ICAM-1 ( p  < .05), VCAM-1 ( p  < .0005), TNF-α ( p  < .005), and vWF ( p  < .005), compared with the controls. In the HIV-infected cohort, VCAM-1 levels were negatively associated with CD4 counts (β = -0.474; p  < .0005), whereas vWF levels were positively associated with viral load (β = 0.344; p  < .01). Levels of ICAM-1 and VCAM-1 were reduced by ART ( p  < .05 vs. baseline for both), however, levels of IL-6, IL-8, and TNF-α increased ( p  < .005 vs. baseline for all). Endothelial activation and inflammation are evident in African ART-naive HIV-infected patients; the former is attenuated, and the latter is increased after 18 months of ART. In HIV-infected subjects, both immunological dysregulation and viral load are associated with biomarkers of endothelial activation.

A number of different viral species are known to have effects on the endothelium. These include dengue, Ebola, Marburg, Lassa fever, yellow fever and influenza viruses, cytomegalovirus and coronaviruses. There are currently seven human endemic coronaviruses, all of which cause respiratory diseases and bind to receptors found within the endothelium. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) is highly infectious. Like its predecessor, SARS-CoV, it binds to angiotensin-converting enzyme-2 (ACE-2), which is expressed in many cell types, particularly in the lung, including endothelial cells. The initiation of a cytokine storm by the virus along with infection of endothelial cells leads to apoptosis and structural and functional changes that attenuate vascular integrity in many organs including the lungs, heart, liver and kidney. Endothelial damage also enhances the coagulation pathway leading to thrombus formation in major vessels and capillaries. Infection with SARS-CoV-2 has an adverse outcome for individuals with particular comorbid diseases, e.g. hypertension, obesity, type 2 diabetes and cardiovascular disease. It is possible that this is due to the presence of pre-existing endothelial dysfunction and systemic inflammation in subjects with these diseases. Therapies for COVID-19 that target the endothelium, the inflammatory response and the coagulation pathway are currently under trial.

Cardiovascular disease (CVD), as a possible consequence of endothelial dysfunction, is prevalent among HIV-infected patients despite successful administration of antiretroviral drugs. This warrants the routine clinical assessment of endothelial function in HIV-positive patients to circumvent potential CVD events. Several different non-invasive strategies have been employed to assess endothelial function in clinical research studies yielding inconsistencies among these reports. This review summarises the different techniques used for assessing endothelial function, with a focus on proposed blood-based biomarkers, such as endothelial leukocyte adhesion molecule-1 (E-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), TNF-α, interleukin 6 (IL6) and soluble thrombomodulin (sTM). The identification of suitable blood-based biomarkers, especially those that can be measured using a point-of-care device, would be more applicable in under-resourced countries where the prevalence of HIV is high.