Plasma tissue factor and immune activation are associated with carotid intima-media thickness progression in treated HIV infection

AIDS. 2020 Mar 15;34(4):519-528. doi: 10.1097/QAD.0000000000002389.


Objectives: We evaluated the roles of biomarkers of immune activation with carotid intima-media thickness (CIMT) progression in treated HIV infection.

Design: Longitudinal observational study of 118 treated and virologically suppressed individuals.

Methods: We measured biomarkers of immune activation at baseline using cryopreserved samples. CIMT was measured at baseline and longitudinally using high-resolution ultrasound. Linear regression was used to estimate biomarker associations with CIMT progression, and logistic regression was used to model plaque progression.

Results: The median duration of follow-up was 2.0 years. The median annual rate of change in mean CIMT was 6.0%. Rates of progression were more rapid in the bifurcation (5.6%/year, P = 0.006) and internal (6.5%/year, P = 0.0008) than common CIMT (4.3%/year). Incident plaque occurred in 13 of the 52 individuals without baseline plaque. In multivariable adjusted analysis, plasma tissue factor and monocyte chemoattractant protein-1 were associated with more rapid common CIMT progression (0.058 mm/year, P = 0.0004 and 0.067 mm/year, P = 0.017; all estimates per doubling). CD8 T-cell count and percentage of HLA-DRCD38CD8 T cells were associated with more rapid internal CIMT progression (0.10 mm/year, P = 0.008 and 0.054 mm/year, P = 0.045). CD8 T-cell count was also associated with 0.068 mm/year more rapid mean CIMT progression (P = 0.011). Each 10% increase in CD4 T-cell count at baseline was associated with a 34% reduced odds of plaque progression (P = 0.018).

Conclusion: Residual immune activation and plasma tissue factor are independently associated with CIMT progression in treated HIV infection. Interventions targeting coagulation and inflammatory pathways to reduce cardiovascular disease risk in HIV merit additional investigations.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • Biomarkers
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carotid Artery Diseases / diagnosis*
  • Carotid Artery Diseases / etiology*
  • Carotid Intima-Media Thickness*
  • Disease Progression
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plasma
  • Risk Factors
  • Thromboplastin / metabolism*


  • Biomarkers
  • Thromboplastin