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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

doi: 10.1097/QAD.0b013e328360e9fb
Epidemiology and Social

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.

aDepartment of Medicine

bDepartment of Global Health, University of Washington, Seattle, Washington, USA

cDepartment of Medical Microbiology, University of Nairobi, Nairobi, Kenya

dS.A. Rotman Laboratories, McLaughlin-Rotman Centre for Global Health, Toronto General Hospital-University Health Network, University of Toronto, Toronto, Ontario, Canada

eUniversity of Nairobi Institute of Tropical and Infectious Diseases (UNITID), College of Health Sciences, University of Nairobi, Nairobi, Kenya

fDepartment of Epidemiology, University of Washington

gDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

hDivision of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Correspondence to Susan M. Graham, MD, MPH, PhD, University of Washington, Box 359909, 325 Ninth Avenue, Seattle, WA 98104-2499, USA. Tel: +1 206 543 4278; fax: +1 206 543 4818; e-mail:

Received 22 December, 2012

Revised 26 February, 2013

Accepted 5 March, 2013

Presented in abstract form at the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, Georgia, 3–6 March 2013.

© 2013 Lippincott Williams & Wilkins, Inc.