title: 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.
abstract: 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]-γ, 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, Th1, and Th17 cytokine levels in IRIS patients precede ART initiation and could help identify patient populations at higher risk for IRIS.
authors.affiliation: Division of Infectious Diseases, Stanford University, Stanford, California 94305–5107, USA. pmgrant@stanford.edu
authors.forename: Philip M
authors.initials: PM
authors.lastname: Grant
authors.forename: Lauren
authors.initials: L
authors.lastname: Komarow
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Zolopa
authors.forename: Janet
authors.initials: J
authors.lastname: Andersen
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Aaron
authors.initials: A
authors.lastname: Richterman
authors.forename: Sudheesh
authors.initials: S
authors.lastname: Kanthikeel
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000378:metabolism*; D016209:Interleukin-8 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016015:Logistic Models; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D016207:Cytokines; D016209:Interleukin-8