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A Longitudinal Study of Changes in Circulating Markers of Endothelial Function in HIV Patients Starting Combination ART
Ulrik Sloth Kristoffersen*1,2, K Kofoed3, G Kronborg3, A K Giger3, A Kjaer1,2, and A M Lebech3
1Rigshospitalet, Copenhagen, Denmark; 2Univ of Copenhagen, Denmark; and 3Hvidovre Univ Hosp, Copenhagen, Denmark
Background: Combination ART (cART), and especially the initiation of this, has
been associated with an increased risk of cardiovascular events. One hypothesis
is that immune reconstitution in connection with initiation of therapy may
cause this. Circulating markers of endothelial dysfunction and atherosclerosis
may be used to assess possible effects on the vessels and have been shown to
correlated with cardiovascular events. The aim of the present study was to
follow the changes in key markers of endothelial function induced by initiation
of ART in a group of treatment naïve HIV+ participants. A control
group of HIV– participants was also included.
Methods: A
total of 115 HIV+ treatment-naive patients from our out-patient
clinic were included. Blood samples were drawn before and after 3 and 12 months
of ART. An age- and gender-matched group of 30 HIV– subjects were
also included. Lipids, standard HIV parameters as well as plasma concentrations of 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-sensitive C-reactive
protein (hs-CRP) were measured using sensitive, fluorescent bead-based
immunoassays. hsCRP was log transformed to obtain normal distribution. Values
are mean ±SEM.
Results: Prior
to treatment, the HIV+ group had elevated levels of sICAM1 (296±24
vs 144±12 ng/mL; p <0.001), t-PAI1 (18,473±1399 vs 5490±576 pg/mL; p
<0.001), and hsCRP (28,060±5530 vs 6665±2063 ng/mL; p <0.001 [log
hsCRP] when compared to controls. In contrast, sVCAM-1 (957±40 vs 876±39 ng/mL;
ns) and E-selectin (17.9±1.1 vs 15.8±1.2 ng/mL; ns) did not differ between the
groups. Initiation of ART caused significantly lower levels levels of
E-selectin (15.1±0.8; p <0.01), sICAM-1 (248±12 ng/mL; p <0.05),
sVCAM-1 (766±33 ng/mL; p <0.001), and hsCRP (14,708±2358 ng/mL; p
<0.001) after 3 months that remained reduced at 12 months. tPAI was not
influenced by initiation of ART (18,065±1208 pg/mL; ns).
Conclusions: Circulating markers of endothelial dysfunction and
pre-atherosclerosis were significantly elevated in treatment-naive HIV patients
compared to healthy controls. Initiation of ART reduced or normalized the
levels of the majority of these markers, an effect that remained at 12 months.
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