title: Quantifying Adaptive and Innate Immune Responses in HIV-Infected Participants Using a Novel High Throughput Assay.
abstract: OBJECTIVE
  HIV infection is characterised by persistent immune dysfunction of both the adaptive and innate immune responses. The aim of this study was to evaluate these responses using a novel high throughput assay in healthy controls and HIV-infected individuals prior to and following anti-retroviral treatment (ART).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Whole blood was assessed using the QuantiFERON Monitor® (QFM) assay containing adaptive and innate immunostimulants. Interferon (IFN)-γ levels (IU/mL) were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  We recruited HIV-infected participants (n = 20 off ART and viremic; n = 59 on suppressive ART) and HIV-uninfected controls (n = 229). Median IFN-γ production was significantly higher in HIV-infected participants compared to controls (IFN-γ 512 vs 223 IU/ml, p<0.0001), but within the HIV-infected participants there was no difference between those on or off ART (median IFN-γ 512 vs 593 IU/ml p = 0.94). Amongst the HIV-infected participants, IFN-γ production was higher in individuals with CD4 count>350 compared to <350 cells/μL (IFN-γ IU/ml 561 vs 259 p = 0.02) and in males compared to females (IFN-γ 542 vs 77 IU/ml p = 0.04). There were no associations between IFN-γ production and age, plasma HIV RNA, nadir CD4 count or duration of HIV infection. Using a multivariable analysis, neither CD4 nor sex were independently predictive of IFN-γ production.
  
  
  CONCLUSIONS
  Using a high throughput assay which assesses both adaptive and innate immune function, we showed elevated IFN-γ production in HIV-infected patients both on and off ART. Further research is warranted to determine if changes in QuantiFERON Monitor® are associated with clinical outcomes.
authors.affiliation: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, Australia.
authors.forename: Michelle K
authors.identifier: http://orcid.org/0000-0002-8692-4145
authors.initials: MK
authors.lastname: Yong
authors.affiliation: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, Australia.
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.affiliation: Centre for Population Health, Burnet Institute, Melbourne, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, Australia.
authors.forename: Julian H
authors.initials: JH
authors.lastname: Elliott
authors.affiliation: Central Clinical School, Monash University and Melbourne Sexual Health Centre, Melbourne, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Fairley
authors.affiliation: QIAGEN, Germantown, Maryland, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Boyle
authors.affiliation: QIAGEN, Germantown, Maryland, United States of America.
authors.forename: Misato
authors.initials: M
authors.lastname: Miyamasu
authors.affiliation: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, Australia.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects* / Q000276:immunology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D057166:High-Throughput Screening Assays; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D007371:Interferon-gamma