PMID- 23734875
OWN - NLM
STAT- MEDLINE
DCOM- 20141113
LR  - 20220331
IS  - 1471-2334 (Electronic)
IS  - 1471-2334 (Linking)
VI  - 13
DP  - 2013 Jun 4
TI  - A prospective study of endothelial activation biomarkers, including plasma 
      angiopoietin-1 and angiopoietin-2, in Kenyan women initiating antiretroviral 
      therapy.
PG  - 263
LID - 10.1186/1471-2334-13-263 [doi]
AB  - 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-naive 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 log10-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/muL). 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.
FAU - Graham, Susan M
AU  - Graham SM
FAU - Rajwans, Nimerta
AU  - Rajwans N
FAU - Tapia, Kenneth A
AU  - Tapia KA
FAU - Jaoko, Walter
AU  - Jaoko W
FAU - Estambale, Benson B A
AU  - Estambale BB
FAU - McClelland, R Scott
AU  - McClelland RS
FAU - Overbaugh, Julie
AU  - Overbaugh J
FAU - Liles, W Conrad
AU  - Liles WC
LA  - eng
GR  - AI-38518/AI/NIAID NIH HHS/United States
GR  - AI-58698/AI/NIAID NIH HHS/United States
GR  - P30 AI027757/AI/NIAID NIH HHS/United States
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130604
PL  - England
TA  - BMC Infect Dis
JT  - BMC infectious diseases
JID - 100968551
RN  - 0 (Angiopoietin-1)
RN  - 0 (Angiopoietin-2)
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cell Adhesion Molecules)
SB  - IM
MH  - Adult
MH  - Angiopoietin-1/*blood
MH  - Angiopoietin-2/*blood
MH  - Anti-Retroviral Agents/*therapeutic use
MH  - Antiretroviral Therapy, Highly Active
MH  - Biomarkers/blood
MH  - Cell Adhesion Molecules/blood
MH  - Female
MH  - HIV Infections/*blood/*drug therapy
MH  - HIV-1/*isolation & purification
MH  - Humans
MH  - Kenya
MH  - Male
MH  - Pregnancy
MH  - Prospective Studies
PMC - PMC3679794
EDAT- 2013/06/06 06:00
MHDA- 2014/11/14 06:00
PMCR- 2013/06/04
CRDT- 2013/06/06 06:00
PHST- 2012/10/11 00:00 [received]
PHST- 2013/06/01 00:00 [accepted]
PHST- 2013/06/06 06:00 [entrez]
PHST- 2013/06/06 06:00 [pubmed]
PHST- 2014/11/14 06:00 [medline]
PHST- 2013/06/04 00:00 [pmc-release]
AID - 1471-2334-13-263 [pii]
AID - 10.1186/1471-2334-13-263 [doi]
PST - epublish
SO  - BMC Infect Dis. 2013 Jun 4;13:263. doi: 10.1186/1471-2334-13-263.