TY - JOUR

T1 - Factors Associated With Plasma IL-6 Levels During HIV Infection

AU - Borges, Álvaro H

AU - O'Connor, Jemma L

AU - Phillips, Andrew N

AU - Rönsholt, Frederikke F

AU - Pett, Sarah

AU - Vjecha, Michael J

AU - French, Martyn A

AU - Lundgren, Jens D

AU - INSIGHT SMART and ESPRIT Study Groups and the SILCAAT Scientific Committee

N1 - © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PY - 2015/8/15

Y1 - 2015/8/15

N2 - 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.

AB - 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.

KW - Adult

KW - Biomarkers

KW - Cross-Sectional Studies

KW - Female

KW - Fibrin Fibrinogen Degradation Products

KW - HIV Infections

KW - Humans

KW - Inflammation

KW - Interleukin-6

KW - Male

KW - Middle Aged

KW - RNA, Viral

KW - Smoking

KW - Viral Load

U2 - 10.1093/infdis/jiv123

DO - 10.1093/infdis/jiv123

M3 - Journal article

C2 - 25722296

VL - 212

SP - 585

EP - 595

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 4

ER -