Factors Associated With Systemic Immune Activation Indices in a Global Primary Cardiovascular Disease Prevention Cohort of People With Human Immunodeficiency Virus on Antiretroviral Therapy

Clin Infect Dis. 2022 Oct 12;75(8):1324-1333. doi: 10.1093/cid/ciac166.


Background: Among antiretroviral therapy (ART)-treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH.

Methods: Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL).

Results: The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels.

Conclusions: Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects.

Clinical trials registration: NCT0234429.

Trial registration: ClinicalTrials.gov NCT00234429.

Keywords: HIV; cardiovascular disease risk; immune activation markers; reproductive aging; women.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cardiovascular Diseases* / complications
  • Female
  • HIV
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Integrases
  • Lipopolysaccharide Receptors
  • Lipoproteins, LDL
  • Male
  • Middle Aged
  • Nucleosides / therapeutic use
  • Reverse Transcriptase Inhibitors / therapeutic use


  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipopolysaccharide Receptors
  • Lipoproteins, LDL
  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • Integrases

Associated data

  • ClinicalTrials.gov/NCT00234429