Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy.
OBJECTIVE
Antiretroviral 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.


METHODS
In 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+/-standard error of the mean.


RESULTS
Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296+/-24 vs. 144+/-12 ng/mL), tPAI-1 (18 473+/-1399 vs. 5490+/-576 pg/mL) and hsCRP (28 060+/-5530 vs. 6665+/-2063 ng/mL) compared with controls (P<0.001). 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+/-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 2 months, which remained reduced at 14 months. tPAI-1 was not influenced by initiation of ART.


CONCLUSIONS
Markers 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.
Kristoffersen
U S
US
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark. ulriksk@mfi.ku.dk
Kofoed
K
K
Kronborg
G
G
Giger
A K
AK
Kjaer
A
A
Lebech
A M
AM
D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012307:Risk Factors; D055815:Young Adult
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D012367:RNA, Viral