Reduction in circulating markers of endothelial dysfunction in HIV‐infected patients during antiretroviral therapy

Abstract

ObjectivesAntiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART. MethodsIn 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean AE standard error of the mean. ResultsPrior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296 AE 24 vs. 144 AE 12 ng/mL), tPAI-1 (18 473 AE 1399 vs. 5490 AE 576 pg/mL) and hsCRP (28 060 AE 5530 vs. 6665 AE 2063 ng/mL) compared with controls (Po0.001). In contrast, sVCAM-1 and E-selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E-selectin (15.1 AE 0.8; Po0.01), sICAM-1 (248 AE 12 ng/mL; Po0.05), sVCAM-1 (766 AE 33 ng/mL; Po0.001) and hsCRP (14 708 AE 2358 ng/mL; Po0.001) after 2 months, which remained reduced at 14 months. tPAI-1 was not influenced by initiation of ART. ConclusionsMarkers of endothelial dysfunction were elevated in treatment-naïve HIV-infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.

Endothelial Dysfunction in HIV

“…A longitudinal study comparing biomarkers in HIV-infected patients at ART initiation to two months and then 14 months into treatment demonstrated a normalization or significant reduction in levels of E-selectin, ICAM-1, VCAM-1 and CRP at the two month interval. These changes persisted up to 14 months except for E-selectin which did not change (Kristoffersen et al, 2009). Similar findings have been reported in other cohort studies, showing significant reductions in both vWF and VCAM-1 levels after six months following initiation of ART, with no demonstrable difference between PI and NNRTI containing regimes (Francisci et al, 2009).…”

Increase in Carotid Artery Intima‐Media Thickness and Arterial Stiffness but Improvement in Several Markers of Endothelial Function after Initiation of Antiretroviral Therapy

“…Therefore, we performed sequential measurements of C-IMT, arterial stiffness, and markers of endothelial function and inflammation in previously treatment-naive patients after the initiation of cART in a randomized clinical trial comparing a regimen of zidovudine/lamivudine/lopinavir/ritonavir (ZDV/3TC/LPV/r) with a nucleoside reverse-transcriptase inhibitor (NRTI)-sparing regimen of nevirapine/LPV/r (NVP/LPV/r). We previously reported that, during 24 months of follow-up, peripheral fat loss, visceral fat accumulation, and insulin resistance developed in the ZDV/3TC/ LPV/r arm, whereas lipid increases were greater in the NVP/ LPV/r arm [15,16]. We hypothesized that, against the background of these regimens having similar effects on the suppression of HIV and immune restoration, these different metabolic profiles might be reflected in different, mainly deleterious effects on the above-mentioned markers of cardiovascular disease risk.…”

Cardiovascular Disease, Statins, and HIV

“…While modern cART efficiently suppresses HIV replication below the limit of detection in blood, promotes CD4 + T-cell recovery and stability, and decreases levels of inflammatory and immune activation markers [3,4], current evidence suggests that viral replication persists, likely within lymphoid organs, through cell-to-cell transmission, and/or through homeostatic proliferation [5][6][7]. Importantly, many markers of inflammation and immune activation are relatively nonspecific, and the precise events driving their production can be challenging to ascertain.…”