期刊
AIDS
卷 27, 期 11, 页码 1803-1813出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e328360e9fb
关键词
angiopoietin-1; angiopoietin-2; endothelial activation; E-selectin; HIV-1; intercellular adhesion molecule-1; vascular cell adhesion molecule-1
资金
- New Investigator Award from the University of Washington Center for AIDS Research
- National Institutes of Health (NIH) [P30 AI027757]
- NIH Institutes and Centers
- NIH [AI-58698, AI-38518]
- Canada Research Chair in Infectious Diseases and Inflammation
- Canadian Institutes for Health Research
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 <200cells/l, 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 log(10) 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.
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