Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy

J Infect Dis. 2016 Feb 1;213(3):370-8. doi: 10.1093/infdis/jiv450. Epub 2015 Sep 7.


Background: Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.

Methods: Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).

Results: A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).

Conclusions: Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.

Keywords: HIV/AIDS; Uganda; aging; antiretroviral therapy; atherosclerosis; carotid intima media thickness; inflammation.

Publication types

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

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Biomarkers / blood
  • Carotid Artery Diseases / epidemiology
  • Carotid Artery Diseases / etiology*
  • Cohort Studies
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation / immunology*
  • HIV Infections / complications*
  • HIV Infections / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Uganda / epidemiology


  • Anti-HIV Agents
  • Antigens, CD
  • Biomarkers
  • Cytokines