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AIDS:
doi: 10.1097/QAD.0b013e328360e9fb
Epidemiology and Social

Endothelial activation biomarkers increase after HIV-1 acquisition: plasma vascular cell adhesion molecule-1 predicts disease progression

Graham, Susan M.a,b,c; Rajwans, Nimertad; Jaoko, Walterc; Estambale, Benson B.A.e; McClelland, R. Scotta,b,c,f; Overbaugh, Julieg; Liles, W. Conrada,d,h

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Abstract

Objective:

We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters.

Design:

HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition.

Methods:

Plasma levels of angiopoietin-1 and angiopoietin-2 (ANG-1, ANG-2) and soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were tested in stored samples from pre-infection, acute infection, and two chronic infection time points. We used nonparametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 <200 cells/μl, stage IV disease, or antiretroviral therapy initiation) or death.

Results:

Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all postinfection periods assessed (P < 0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (P = 0.0001), and ANG-1 decreased in chronic infection (P = 0.0004). Among 228 participants followed over 1028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (adjusted hazard ratio 5.36, 95% confidence interval 1.99–14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels.

Conclusion:

HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 postinfection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

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