Background: HIV infection carries an increased risk of cardiovascular disease. Endothelial dysfunction and chronic inflammation have been separately reported in HIV⁺ subjects. It is unclear whether lipoatrophy is independently associated with increased endothelial dysfunction and higher systemic inflammation. We assessed endothelial activation and inflammation markers in HIV⁺ subjects, and their relationship with limb fat and metabolic parameters.
Methods: We enrolled 82 patients with lipoatrophy (lipo⁺ group) and 50 HIV⁺ on ART for >2 years without lipoatrophy with HIV-1 RNA <1000 copies/mL (lipo^– group), 20 HIV⁺ ART-naïve and 30 HIV^– healthy controls. Plasma levels of tumor necrosis factor (TNF) -a, soluble TNF receptors (sTNFRI, sTNFRII), interleukin (IL) -6, and high-sensitivity C-reactive protein (hsCRP) were measured as well as levels of 3 endothelial markers:  soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and the established cardiovascular marker myeloperoxidase (MPO). Fasting metabolic profile was also measured. Wilcoxon rank sum tests and Spearman Rank correlation coefficients were used.
Results:  Of the participants, 41% were white and 72% male. Age was similar in HIV⁺ naïve and HIV^–, but HIV⁺ on ART were older than naïve (45 vs 31 years; p <0.001). All groups had similar body mass index. sICAM-1, sVCAM-1, and vWF were higher in HIV⁺ naïve patients than HIV^– (vWF 28.9 vs 12.1 U/mL; p = 0.003) and to HIV⁺ on ART (vWF 28.9 vs 16.8 U/mL; p = 0.03), but no difference was found between lipo⁺ and lipo^– groups, or between HIV⁺ on ART and HIV^– controls. DEXA-measured limb fat did not correlate with any endothelial marker. Plasma TNF-a, hsCRP, and IL-6 were similar in all groups. sTNFRI and sTNFRII were similar in HIV⁺ naïve vs HIV^– (p = 0.89), but were lower in treated vs naïve group (sTNFRII 294 vs 600 pg/mL; p = 0.004). Lipo⁺ group had lower sTNFRI and II than matched lipo^– group (sTNFRII 238 vs 330 pg/mL; p = 0.02). MPO was significantly higher in HIV⁺ naïve than HIV^– (5590 vs 1684 pg/mL; p = 0.005), but similar in HIV⁺ treated and naïve. MPO significantly correlated with sICAM-1, sVCAM-1, and sTNFRII. None of the endothelial nor inflammation markers correlated with CD4 count, lipids, glucose, or specific ART type.
Conclusions: This study shows enhanced endothelial activation and increased cardiovascular markers in ART-naïve, while HIV⁺ on ART with HIV-1 RNA <1000 copies/mL have similar values to HIV^– of similar age. Lipoatrophy status did not influence these findings.