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

AIDS. 2013 Jul 17;27(11):1803-13. doi: 10.1097/QAD.0b013e328360e9fb.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiopoietin-1 / blood
  • Angiopoietin-2 / blood
  • Biomarkers / blood*
  • CD4 Lymphocyte Count
  • Disease Progression
  • E-Selectin / blood
  • Female
  • Follow-Up Studies
  • HIV Infections / pathology*
  • HIV Infections / virology
  • HIV-1 / isolation & purification
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Kenya
  • Plasma / chemistry
  • Prospective Studies
  • Survival Analysis
  • Vascular Cell Adhesion Molecule-1 / blood*


  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers
  • E-Selectin
  • SELE protein, human
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1