HIV is associated with endothelial activation despite ART, in a sub-Saharan African setting

Abstract

ObjectiveTo study the relationship between endothelial dysfunction, HIV infection, and stroke in Malawians.MethodsUsing a cross-sectional design, we measured plasma levels of intercellular adhesion molecule-1 (ICAM-1), plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), and soluble thrombomodulin (sTM) in stroke patients and controls, stratified by HIV status. These biomarkers were measured using ELISA. After dichotomization, each biomarker was used as the dependent variable in a multivariable logistic regression model. Primary independent variables included HIV and stroke status. Adjustment variables were age, sex, hypertension, diabetes mellitus, tobacco and alcohol consumption, personal/family history of stroke, antiretroviral therapy status, and hypercholesterolemia.ResultsSixty-one stroke cases (19 HIV+) and 168 controls (32 HIV+) were enrolled. The median age was 55 years (38.5–65.0) for controls and 52 years (38.0–73.0) for cases (p = 0.38). The median CD4+ T-cell count was 260.1 cells/mm3 (156.3–363.9) and 452 cells/mm3 (378.1–527.4) in HIV-infected cases and controls, respectively. HIV infection was independently associated with high levels of ICAM-1 (OR = 3.6, 95% CI: 1.3–10.6, p = 0.018) in controls but not in stroke cases even after excluding patients with a viral load >1,000 RNA copies/mL (OR = 4.1, 95% CI: 1.3–13.1, p = 0.017). There was no association between the clinical profiles of HIV-positive controls or HIV-positive stroke and high levels of PAI-1, VEGF, and sTM.ConclusionsHIV infection is associated with endothelial activation despite antiretroviral treatment. Our findings underscore the need for larger clinical cohorts to better understand the contribution of this perturbation of the endothelial function to the increasing burden of cardiovascular diseases in sub-Saharan Africa.

Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-1/Mtb Co-infected Persons

“…Vascular endothelial growth factor-D (VEGF-D) is a secreted protein that can promote the remodeling of blood vessels and lymphatics in development and disease ( 35 ). While their increase could indicate normalization of endothelial integrity and activity on ART, recent evidence suggests that HIV-1 associated endothelial activation persists despite ART ( 36 ). Due to increased rates of cardiovascular disease among people living with HIV-1, this is an important area to explore in further studies.…”

Trends and Clinical Characteristics of HIV and Cerebrovascular Disease in Low- and Middle-Income Countries (LMICs) Between 1990 and 2021

“…Viral load was rarely described. Kamtchum-Tatuene et al reported a median viral load of 1,884 copies/ml, with 55.6% of participants having > 1,000 copies/ml; while in a South African study, 62.5% of patients were not virologically suppressed, despite many patients reporting being on ART [ 31 , 32 ]. The use of ART was well described, and as shown in Table 2 , coverage was generally poor (i.e.…”

Antiretroviral treatment-induced decrease in immune activation contributes to reduced susceptibility to tuberculosis in HIV-1-TB co-infected persons

“…Vascular endothelial growth factor-D (VEGF-D) is a secreted protein that can promote the remodeling of blood vessels and lymphatics in development and disease (22). While their increase could indicate normalisation of endothelial integrity and activity on ART, recent evidence suggests that HIV-1 associated endothelial activation persists despite ART (23). Due to increased rates of cardiovascular disease among people living with HIV-1, this is an important area to explore in further studies.…”