Factors Associated With Plasma IL-6 Levels During HIV Infection

J Infect Dis. 2015 Aug 15;212(4):585-95. doi: 10.1093/infdis/jiv123. Epub 2015 Feb 26.


Background: Elevated interleukin 6 (IL-6) levels have been linked to cardiovascular disease, cancer and death. Persons with human immunodeficiency virus (HIV) infection receiving treatment have higher IL-6 levels, but few data are available on factors associated with circulating IL-6.

Methods: Participants in 3 trials with IL-6 measured at baseline were included (N = 9864). Factors associated with IL-6 were identified by linear regression. Demographic and HIV variables (nadir/entry CD4(+) cell count, HIV RNA level, antiretroviral therapy regimen) were investigated in all 3 trials. In the SMART (Strategies for Management of Anti-Retroviral Therapy) trial, CD4/CD8 ratio, smoking, comorbid conditions, serum lipids, renal function (estimated glomerular filtration rate [eGFR]), and educational level were assessed.

Results: Demographics associated with higher IL-6 levels were older age and lower education, whereas black race was associated with lower IL-6. Higher HIV RNA levels were associated with higher IL-6 levels, and higher nadir CD4(+) cell counts with lower IL-6 levels. Compared with efavirenz, protease inhibitors were associated with higher and nevirapine with lower IL-6 levels. Smoking and all comorbid conditions were related to higher IL-6. IL-6 levels increased with decreasing eGFR and decreasing serum lipids.

Conclusions: Higher levels of IL-6 were associated with older age, nonblack race, higher body mass index, lower serum lipid levels, HIV replication, low nadir CD4(+) cell count, protease inhibitor use, comorbid conditions, and decreased eGFR. Multiple factors affect inflammation in HIV and should be considered in studies of IL-6 as a biomarker of clinical outcomes.

Keywords: HIV; IL-6; cancer; cardiovascular disease; inflammation.

Publication types

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

MeSH terms

  • Adult
  • Biomarkers
  • Cross-Sectional Studies
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • HIV Infections / blood*
  • HIV Infections / complications
  • HIV Infections / metabolism
  • Humans
  • Inflammation / metabolism
  • Interleukin-6 / blood*
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Smoking
  • Viral Load


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Interleukin-6
  • RNA, Viral
  • fibrin fragment D