title: The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection.
abstract: OBJECTIVE
  Monocyte activation, endothelial dysfunction and platelet activation all potentially contribute to the increased risk of cardiovascular disease (CVD) reported in those with HIV-1 infection. To date, no study has examined how initiation of antiretroviral therapy (ART) affects markers of all three processes. We aimed to compare markers of monocyte, endothelial and platelet function between untreated HIV-positive subjects and HIV-negative controls and to examine the early effects of ART initiation on these markers.
  
  
  METHODS
  We measured monocyte [soluble CD14 (sCD14) and sCD163], endothelial [von Willebrand factor (vWF), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1)] and platelet [soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L) and soluble glycoprotein VI (sGPVI)] biomarkers before and at weeks 4 and 12 post ART initiation in HIV-positive and well-matched HIV-negative controls.
  
  
  RESULTS
  We examined 40 subjects, 25 HIV-positive subjects and 15 controls, with a median age of 34 years [interquartile range (IQR) 31, 40 years], of whom 60% were male and 47.5% Caucasian. Pre-ART, all biomarkers (monocyte, endothelial and platelet) were significantly higher in HIV-positive patients versus controls (all P < 0.05) and decreased with ART initiation, except for sCD14, which remained unchanged [median 1680 (IQR 1489, 1946) ng/mL at week 12 versus 1570 (IQR 1287, 2102) ng/mL at week 0; P = 0.7]. Although platelet activation markers reduced to levels comparable to those in controls, endothelial dysfunction markers remained elevated, as did sCD163 [at week 12, median 1005 (IQR 791, 1577) ng/mL in HIV-positive patients versus 621 (IQR 406, 700) ng/mL in controls; P < 0.0001].
  
  
  CONCLUSIONS
  ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: J A
authors.initials: JA
authors.lastname: O'Halloran
authors.affiliation: Cardiovascular Biology Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Dunne
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Mmp
authors.initials: M
authors.lastname: Gurwith
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: J S
authors.initials: JS
authors.lastname: Lambert
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: G J
authors.initials: GJ
authors.lastname: Sheehan
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: E R
authors.initials: ER
authors.lastname: Feeney
authors.affiliation: HIV Directorate, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pozniak
authors.affiliation: Department of Global Health and Stichting HIV Monitoring, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Cardiovascular Biology Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Kenny
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Pwg
authors.initials: P
authors.lastname: Mallon
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D015415:Biomarkers
keywords: HIV; cardiovascular disease; endothelial dysfunction; monocyte activation; platelet function