Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People With HIV and HIV-Negative Adults in Kenya

Abstract

Background Residual monocyte activation may contribute to increased risk for endothelial dysfunction and subsequent atherosclerotic cardiovascular diseases (CVD) among people with HIV (PWH) on antiretroviral therapy (ART). We examined the relationship between monocyte activation and endothelial activation in PWH in Kenya. Methods Serum levels of markers of endothelial activation (soluble/circulating intercellular [sICAM-1] and vascular [sVCAM-1] cell adhesion molecules-1), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and monocyte activation (soluble CD14 [sCD14]) were measured in 275 PWH on ART and 266 HIV-negative persons. Linear regression was used to evaluate associations adjusting for demographic and traditional CVD risk factors. Results Among 541 participants, median age was 43 years, 50% were female, and most PWH were virally suppressed (97%). sICAM-1 and sVCAM-1 levels were significantly higher in PWH than in HIV-negative participants (p&0.001 for both). After further adjustment for traditional CVD risk factors, HIV-infection remained associated with 49% (95% CI:33%, 67%) greater sICAM-1 and 30% (95% CI:14%, 48%) greater sVCAM-1 relative to uninfected controls. Adjustment for sCD14 substantially attenuated the difference between PWH and HIV-negative individuals. In a stratified analysis of PWH, both sICAM-1 and sVCAM-1 were positively associated with sCD14 (p&0.001). Conclusion Despite viral suppression, African PWH have evidence of enhanced endothelial activation associated with sCD14 suggesting that monocyte activation plays a role in atherosclerotic plaque development. Future studies are needed to determine mechanistic pathways leading to monocyte activation in this population.

Increased endothelial biomarkers are associated with HIV antiretroviral therapy and C-reactive protein among a African rural population in Limpopo Province, South Africa

“…The association between HIV infection and L-selectin in the current study may be attributed to chronic inflammation. Chronic HIV inflammation is known to induce endothelial activation and it has been suggested as a possible mechanism for HIVinduced atherosclerosis (22,42). Further, in the current study, CRP was positively associated with increased Lselectin, which may reiterate the role of inflammation in endothelial activation.…”

Brief Report: Evaluation of Inflammation and Atherogenesis Biomarkers Through 148 Weeks Postswitch to Dolutegravir and Rilpivirine in SWORD-1/SWORD-2

“…6 Biomarkers of inflammation [eg, C-reactive protein (CRP) and interleukin-6 (IL-6)], monocyte and macrophage activation [eg, soluble CD14 (sCD14) and soluble CD163 (sCD163)], hypercoagulation (eg, D-dimer), intestinal barrier dysfunction [eg, fatty acid-binding protein-2 (FABP-2)], and endothelial dysfunction [eg, soluble vascular cell adhesion molecule-1 (sVCAM-1)] are independent predictors of mortality in PLWH. [6][7][8] We evaluated biomarkers of inflammation and atherogenesis through 148 weeks postswitch from the 3-drug or 4-drug CAR to the 2-drug regimen dolutegravir + rilpivirine in the SWORD-1 and SWORD-2 studies.…”

Changes in Inflammatory and Atherogenesis Biomarkers With the 2-Drug Regimen Dolutegravir Plus Lamivudine in Antiretroviral Therapy–Experienced, Virologically Suppressed People With HIV-1: A Systematic Literature Review

“…Observations from the Strategies for Management of Anti-Retroviral Therapy (SMART) study showed that elevated baseline levels of inflammatory biomarkers were independently associated with increased risk of cardiovascular disease and mortality [ 9 , 10 ]. Mediators of other immunological processes such as intestinal barrier dysfunction (eg, fatty acid binding protein-2 [FABP-2]) and endothelial dysfunction (eg, soluble vascular cell adhesion molecule-1 [sVCAM-1]) have also been assessed as biomarkers of inflammation in HIV [ 5 , 11 ]. Furthermore, persistently low CD4 + /CD8 + ratio (≤0.4) has been associated with systemic inflammation in ART-treated PWH, which may be linked to an increased risk of non-AIDS-defining morbidity and mortality [ 7 , 12 ].…”