Factors Associated With Plasma IL-6 Levels During HIV Infection.
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.
Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
Álvaro H
ÁH
Borges
Research Department of Infection and Population Health, University College London, United Kingdom.
Jemma L
JL
O'Connor
Research Department of Infection and Population Health, University College London, United Kingdom.
Andrew N
AN
Phillips
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
Frederikke F
FF
Rönsholt
Research Department of Infection and Population Health, University College London, United Kingdom MRC Clinical Trials Unit, University College London, United Kingdom Kirby Institute, University of New South Wales Australia, Sydney.
Sarah
S
Pett
Institute for Clinical Research, Inc., Veterans Affairs Medical Center, Washington, District of Columbia.
Michael J
MJ
Vjecha
School of Pathology and Laboratory Medicine, University of Western Australia Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine, Australia.
Martyn A
MA
French
Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
Jens D
JD
Lundgren
D000328:Adult; D015415:Biomarkers; D003430:Cross-Sectional Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012907:Smoking; D019562:Viral Load
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D012367:RNA, Viral; C036309:fibrin fragment D
HIV; IL-6; cancer; cardiovascular disease; inflammation