Biomarkers of Endothelial Activation in Black South African HIV-Positive Subjects are Associated with Both High Viral Load and Low CD4 Counts.

Abstract

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/mm3 and 42 subjects with CD4 count >350 cells/mm3), 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.