Endothelial Activation Markers Are Linked to HIV Status and Are Independent of Antiretroviral Therapy and Lipoatrophy

Abstract

Objectives To assess the association of inflammatory and endothelial activation biomarkers with the presence of lipoatrophy in HIV-infected subjects and to examine the role of HIV, antiretroviral therapy (ART), and metabolic parameters in endothelial activation and inflammation. Design Prospective, cross-sectional study including 4 groups: HIV+ on ART with HIV-1 RNA <1000 copies/mL with and without clinical lipoatrophy, HIV+ ART naive, and healthy controls. Methods We measured plasma levels of inflammatory cytokines (tumor necrosis factor-α, soluble tumor necrosis factor receptors I and II, interleukin-6, C-reactive protein, and myeloperoxidase) and endothelial activation markers (soluble intercellular and vascular cell adhesion molecules and von Willebrand factor). Results We enrolled 182 subjects. Limb fat and lipoatrophy status were not correlated with endothelial markers. Endothelial markers were higher in HIV+ ART naive when compared with healthy controls and with HIV+ on ART but were similar between HIV+ on ART and healthy controls. Neither endothelial nor inflammatory markers were correlated with HIV duration, CD4 count, lipids, glucose, or specific ART. Strong correlations were found between some inflammatory cytokines and endothelial markers. Conclusions There is enhanced endothelial activation in ART naive, whereas HIV+ on ART has similar values to healthy controls. Lipoatrophy did not seem to affect endothelial activation. Results highlight a potential association between heightened inflammation and endothelial activation.

Relationship of Body Composition, Metabolic Status, Antiretroviral Use, and HIV Disease Factors to Endothelial Dysfunction in HIV-Infected Subjects

“…A recent study found a potential association between heightened circulating inflammatory markers and markers of endothelial activation, 27 but our study using brachial FMD showed no such associations with inflammatory markers. Indeed, we did not show a correlation of circulating markers of endothelial activation with our physiologic measure of endothelial function.…”

“…8 More contemporary studies in which few subjects received indinavir have failed to confirm a role for PI-containing antiretroviral regimens in endothelial dysfunction 14 or endothelial activation. 27 In fact, there was a nonsignificant trend for better endothelial function measured by brachial FMD among subjects receiving PIs (predominantly nelfinavir and lopinavir-ritonavir) in the study of Solages and colleagues.…”

Higher Plasma Myeloperoxidase Levels Are Not Associated with an Increased Risk for Cardiovascular Events in HIV-Infected Adults

“…This is consistent with recent findings of a close relationship between inflammation due to uncontrolled viremia/advanced HIV disease and a higher risk of CV disease and endothelial dysfunction. [11][12][13] As ART prolongs the lives of HIV-infected adults, understanding the pathogenesis of CV disease in this population is essential. Further studies are needed to explore the role of MPO in HIV-infected adults and establish useful biochemical markers in this high-risk group.…”

Serum activities of oxidative burst enzymes in HIV infected subjects

“…It was reported that myeloperoxidase activity was significantly higher in HIV infected subjects on HAART than HAART naïve subjects [22]. But Ross et al [23] observed elevated myeloperoxidase activity in HIV infected adults both on HAART and HAART naïve. In HIV infection, the expected and appropriate inflammatory response to an infectious process may be amplified and the risk of secondary infection increases.…”