TY - JOUR
T1 - Inflammatory Biomarkers and Mortality Risk among HIV-Suppressed Men
T2 - A Multisite Prospective Cohort Study
AU - Wada, Nikolas I.
AU - Bream, Jay H.
AU - Martínez-Maza, Otoniel
AU - Macatangay, Bernard
AU - Galvin, Shannon R.
AU - Margolick, Joseph B.
AU - Jacobson, Lisa P.
N1 - Funding Information:
Financial support. Data in this manuscript were collected by the MACS, funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute of Mental Health. MACS sites are Johns Hopkins University Bloomberg School of Public Health (principal investigator [PI], J. B. M.; grant U01- AI35042); Northwestern University (PI, Steven Wolinsky; grant U01- AI35039); University of California, Los Angeles (PI, Roger Detels; grant U01-AI35040); University of Pittsburgh (PI, Charles Rinaldo; grant U01- AI35041); and the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (PI, L. P. J.; grant UM1-AI35043). MACS data collection is also supported by from the a grant from the National Center for Advancing Translational Sciences, a component of the NIH, and NIH Roadmap for Medical Research (grant UL1-TR001079 to Johns Hopkins Institute for Clinical and Translational Research). The research was also supported by the Human Immunodeficiency Virus Prevention Trials Network, sponsored by the NIAID, the National Institute on Drug Abuse, the National Institute of Mental Health, and the Office of AIDS Research, NIH (grant UM1-AI068613).
Publisher Copyright:
© 2016 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Background. Human immunodeficiency virus (HIV)-induced inflammation and immune activation persist after initiation of combination antiretroviral therapy (cART) and HIV suppression and may contribute to mortality risks that exceed those in HIV-uninfected populations, though associations are unclear. Methods. In the prospective Multicenter AIDS Cohort Study, comprising men who have sex with men from Baltimore, Chicago, Los Angeles, and Pittsburgh, concentrations of 24 biomarkers of inflammation and immune activation were measured in stored serum from HIV-positive men obtained after cART-induced HIV suppression between 1996 and 2009. The outcome was nonaccidental death, with follow-up until 2014. We used Cox proportional hazards models to test whether biomarker concentrations predict time from HIV suppression to death and adjusted for multiple tests. Exploratory factor analysis (EFA) was employed to identify groupings of biomarkers that predict mortality risk. Results. Of 670 men followed up from HIV suppression, 54 died by the end of 2013. After adjustment for age, CD4+ cell count, hepatitis B or C virus infection, and smoking, concentrations in the highest quartile of 4 biomarkers were significantly associated with mortality risk after controlling the false discovery rate at 5%: interleukin (IL) 6 (hazard ratio, 3.54; 95% confidence interval, 2.06-6.10), soluble IL 2Rα (3.29, 1.85-5.85), soluble CD14 (2.67, 1.55-4.61), and chemokine (CXC motif) ligand 13 (CXCL13; 2.26; 1.29-3.95). EFA yielded 2 biomarker groupings that were independent predictors of mortality risk. Conclusions. Despite having undetectable HIV RNA levels during cART, men with higher concentrations of several biomarkers (particularly IL 6, soluble IL 2Rα, soluble CD14, and CXCL13) had higher hazards of long-term mortality. Correlations observed among biomarker concentrations may represent underlying inflammatory processes that contribute to mortality risk.
AB - Background. Human immunodeficiency virus (HIV)-induced inflammation and immune activation persist after initiation of combination antiretroviral therapy (cART) and HIV suppression and may contribute to mortality risks that exceed those in HIV-uninfected populations, though associations are unclear. Methods. In the prospective Multicenter AIDS Cohort Study, comprising men who have sex with men from Baltimore, Chicago, Los Angeles, and Pittsburgh, concentrations of 24 biomarkers of inflammation and immune activation were measured in stored serum from HIV-positive men obtained after cART-induced HIV suppression between 1996 and 2009. The outcome was nonaccidental death, with follow-up until 2014. We used Cox proportional hazards models to test whether biomarker concentrations predict time from HIV suppression to death and adjusted for multiple tests. Exploratory factor analysis (EFA) was employed to identify groupings of biomarkers that predict mortality risk. Results. Of 670 men followed up from HIV suppression, 54 died by the end of 2013. After adjustment for age, CD4+ cell count, hepatitis B or C virus infection, and smoking, concentrations in the highest quartile of 4 biomarkers were significantly associated with mortality risk after controlling the false discovery rate at 5%: interleukin (IL) 6 (hazard ratio, 3.54; 95% confidence interval, 2.06-6.10), soluble IL 2Rα (3.29, 1.85-5.85), soluble CD14 (2.67, 1.55-4.61), and chemokine (CXC motif) ligand 13 (CXCL13; 2.26; 1.29-3.95). EFA yielded 2 biomarker groupings that were independent predictors of mortality risk. Conclusions. Despite having undetectable HIV RNA levels during cART, men with higher concentrations of several biomarkers (particularly IL 6, soluble IL 2Rα, soluble CD14, and CXCL13) had higher hazards of long-term mortality. Correlations observed among biomarker concentrations may represent underlying inflammatory processes that contribute to mortality risk.
KW - HIV
KW - biomarkers
KW - cART
KW - inflammation
KW - mortality
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U2 - 10.1093/cid/ciw409
DO - 10.1093/cid/ciw409
M3 - Article
C2 - 27343547
AN - SCOPUS:84990914052
SN - 1058-4838
VL - 63
SP - 984
EP - 990
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 7
ER -