期刊
BMC INFECTIOUS DISEASES
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2334-13-263
关键词
HIV-1; HAART; ICAM-1; VCAM-1; E-selectin; Angiopoietin-1; Angiopoietin-2; Endothelium
资金
- University of Washington Center for AIDS Research
- National Institutes of Health (NIH) [P30 AI027757]
- NIH (National Institute of Allergy and Infectious Diseases)
- NIH (National Cancer Institute)
- NIH (National Institute of Mental Health)
- NIH (National Institute on Drug Abuse)
- NIH (National Institute of Child Health & Human Development)
- NIH (National Heart, Lung, and Blood Institute)
- NIH (National Institute on Aging)
- NIH [AI-58698, AI-38518]
- Canada Research Chair in Infectious Diseases and Inflammation from the Canadian Institutes for Health Research
Background: HIV-1-related inflammation is associated with increased levels of biomarkers of vascular adhesion and endothelial activation, and may increase production of the inflammatory protein angiopoietin-2 (ANG-2), an adverse prognostic biomarker in severe systemic infection. We hypothesized that antiretroviral therapy (ART) initiation would decrease endothelial activation, reducing plasma levels of ANG-2. Methods: Antiretroviral nave Kenyan women with advanced HIV infection were followed prospectively. Endothelial activation biomarkers including soluble intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, and plasma ANG-2 and angiopoietin-1 (ANG-1) were tested in stored plasma samples from 0, 6, and 12 months after ART initiation. We used Wilcoxon matched-pairs signed rank tests to compare endothelial activation biomarkers across time-points, generalized estimating equations to analyze associations with change in log(10)-transformed biomarkers after ART initiation, and Cox proportional-hazards regression to analyze associations with mortality. Results: The 102 HIV-1-seropositive women studied had advanced infection (median CD4 count, 124 cells/mu L). Soluble ICAM-1 and plasma ANG-2 levels decreased at both time-points after ART initiation, with concomitant increases in the beneficial protein ANG-1. Higher ANG-2 levels after ART initiation were associated with higher plasma HIV-1 RNA, oral contraceptive pill use, pregnancy, severe malnutrition, and tuberculosis. Baseline ANG-2 levels were higher among five women who died after ART initiation than among women who did not (median 2.85 ng/mL [ inter-quartile range (IQR) 2.47-5.74 ng/mL] versus median 1.32 ng/mL [ IQR 0.35-2.18 ng/mL], p = 0.01). Both soluble ICAM-1 and plasma ANG-2 levels predicted mortality after ART initiation. Conclusions: Biomarkers of endothelial activation decreased after ART initiation in women with advanced HIV-1 infection. Changes in plasma ANG-2 were associated with HIV-1 RNA levels over 12 months of follow-up. Soluble ICAM-1 and plasma ANG-2 levels represent potential biomarkers for adverse outcomes in advanced HIV-1 infection.
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