The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection

HIV Med. 2015 Nov;16(10):608-19. doi: 10.1111/hiv.12270. Epub 2015 Jun 25.

Abstract

Objectives: 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.

Keywords: HIV; cardiovascular disease; endothelial dysfunction; monocyte activation; platelet function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Platelets / physiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Case-Control Studies
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / physiology

Substances

  • Biomarkers