Factors Associated With Plasma IL-6 Levels During HIV Infection

• Published in: The Journal of infectious diseases Vol. 212; no. 4; pp. 585 - 595
• Main Authors: Borges, Álvaro H., O'Connor, Jemma L., Phillips, Andrew N., Rönsholt, Frederikke F., Pett, Sarah, Vjecha, Michael J., French, Martyn A., Lundgren, Jens D.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15-08-2015
• Subjects: Adult; Biomarkers; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products - metabolism; HIV Infections - blood; HIV Infections - complications; HIV Infections - metabolism; HIV/AIDS; Humans; Inflammation - metabolism; Interleukin-6 - blood; Interleukin-6 - metabolism; Major and Brief Reports; Male; Middle Aged; RNA, Viral - blood; Smoking; Viral Load; cardiovascular disease; cancer; HIV; inflammation; IL-6
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiv123

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.