Elevated Interleukin 8 and T-Helper 1 and T-Helper 17 Cytokine Levels Prior to Antiretroviral Therapy in Participants Who Developed Immune Reconstitution Inflammatory Syndrome During ACTG A5164

Background. Immune reconstitution inflammatory syndrome (IRIS) reflects an aberrant immune response that can develop in human immunodeficiency virus-infected patients initiating antiretroviral therapy (ART). Its pathogenesis remains unclear. Methods. We performed a nested case-control study using sp...

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Bibliographic Details
Published in:The Journal of infectious diseases 2012-12, Vol.206 (11), p.1715-1723
Main Authors: Grant, Philip M., Komarow, Lauren, Lederman, Michael M., Pahwa, Savita, Zolopa, Andrew R., Andersen, Janet, Asmuth, David M., Devaraj, Sridevi, Pollard, Richard B., Richterman, Aaron, Kanthikeel, Sudheesh, Sereti, Irini
Format: Article
Language:English
Subjects:
Adult
AIDS
Anti-HIV Agents - adverse effects
Anti-HIV Agents - therapeutic use
Antiretrovirals
Arts
Biological and medical sciences
Biological markers
Biomarkers
Case-Control Studies
Corticosteroids
Cytokines
Cytokines - blood
Cytokines - genetics
Cytokines - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Gene Expression Regulation - immunology
HIV
HIV Infections - drug therapy
HIV/AIDS
Humans
Immune Reconstitution Inflammatory Syndrome - metabolism
Immunology
Infectious diseases
Interleukin-8 - blood
Interleukin-8 - genetics
Interleukin-8 - metabolism
Logistic Models
Major and Brief Reports
Medical sciences
Microbiology
Middle Aged
Risk Factors
T lymphocytes
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Summary:Background. Immune reconstitution inflammatory syndrome (IRIS) reflects an aberrant immune response that can develop in human immunodeficiency virus-infected patients initiating antiretroviral therapy (ART). Its pathogenesis remains unclear. Methods. We performed a nested case-control study using specimens from ACTG A5164. We compared plasma biomarkers and T-cell subsets in 19 IRIS and 39 control participants at study entry, ART initiation, and IRIS and used conditional logistic regression to develop IRIS predictive models. We evaluated the effect of corticosteroids on biomarker levels. Results. Eleven and 8 participants developed paradoxical and unmasking IRIS, respectively, none while still receiving corticosteroids. Compared to controls, cases displayed elevations at study entry in interleukin (IL) 8, T-helper (Th) 1 (IL-2, interferon [IFN]-y, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN-γ and TNF were strong predictors of IRIS. Participants who received corticosteroids and later developed IRIS had marked increases in IL-6, IL-8, and IFN-γ at the time of IRIS. T-cell activation markers did not differ in cases and controls prior to ART but were increased in cases at the time of IRIS. Conclusions. Increased IL-8, Thl, and Th17 cytokine levels in IRIS patients precede ART initiation and could help identify patient populations at higher risk for IRIS.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jis604