Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy

Mark J. Siedner, June Ho Kim, Ruth Sentongo Nakku, Prossy Bibangambah, Linda Hemphill, Virginia A. Triant, Jessica E. Haberer, Jeffrey N. Martin, A. Rain Mocello, Yap Boum, Douglas S. Kwon, Russell P. Tracy, Tricia Burdo, Yong Huang, Huyen Cao, Samson Okello, David Bangsberg, Peter W. Hunt

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalJournal of Infectious Diseases
Volume213
Issue number3
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • aging
  • antiretroviral therapy
  • atherosclerosis
  • carotid intima media thickness
  • HIV/AIDS
  • inflammation
  • Uganda

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

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    Siedner, M. J., Kim, J. H., Nakku, R. S., Bibangambah, P., Hemphill, L., Triant, V. A., Haberer, J. E., Martin, J. N., Mocello, A. R., Boum, Y., Kwon, D. S., Tracy, R. P., Burdo, T., Huang, Y., Cao, H., Okello, S., Bangsberg, D., & Hunt, P. W. (2016). Persistent immune activation and carotid atherosclerosis in HIV-infected ugandans receiving antiretroviral therapy. Journal of Infectious Diseases, 213(3), 370-378. https://doi.org/10.1093/infdis/jiv450