title: Polyantigenic interferon-γ responses are associated with protection from TB among HIV-infected adults with childhood BCG immunization.
abstract: BACKGROUND
  Surrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified.
  
  
  METHODS
  HIV-infected adults with childhood BCG immunization entering the placebo arm of the DarDar TB vaccine trial in Dar es Salaam, Tanzania, were assessed for interferon gamma (IFN-γ) responses to three mycobacterial antigen preparations--secreted Mycobacterium tuberculosis antigens 85 (Ag85), early secretory antigenic target 6 (ESAT-6) and polyantigenic whole cell lysate (WCL). We investigated the association between the number of detectable IFN-γ responses at baseline and the subsequent risk of HIV-associated TB.
  
  
  RESULTS
  During a median follow-up of 3.3 years, 92 (9.4%) of 979 placebo recipients developed TB. The incidence of TB was 14% in subjects with no detectable baseline IFN-γ responses vs. 8% in subjects with response to polyantigenic WCL (P = 0.028). Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB. Overall the percentage of subjects with 0, 1, 2 and 3 baseline IFN-γ responses to mycobacterial preparations who developed HIV-associated TB was 14%, 8%, 7% and 4%, respectively (P = 0.004). In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001).
  
  
  CONCLUSIONS
  Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT0052195.
authors.affiliation: Dartmouth Medical School, Lebanon, New Hampshire, United States of America. Timothy.Lahey@Dartmouth.edu
authors.forename: Timothy
authors.initials: T
authors.lastname: Lahey
authors.forename: Brian K
authors.initials: BK
authors.lastname: Mitchell
authors.forename: Robert D
authors.initials: RD
authors.lastname: Arbeit
authors.forename: Siddharth
authors.initials: S
authors.lastname: Sheth
authors.forename: Mecky
authors.initials: M
authors.lastname: Matee
authors.forename: C Robert
authors.initials: CR
authors.lastname: Horsburgh
authors.forename: Todd
authors.initials: T
authors.lastname: MacKenzie
authors.forename: Lillian
authors.initials: L
authors.lastname: Mtei
authors.forename: Muhammad
authors.initials: M
authors.lastname: Bakari
authors.forename: Jenni M
authors.initials: JM
authors.lastname: Vuola
authors.forename: Kisali
authors.initials: K
authors.lastname: Pallangyo
authors.forename: C Fordham
authors.initials: CF
authors.lastname: von Reyn
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D002648:Child; D016208:Databases, Factual; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D015999:Multivariate Analysis; D009163:Mycobacterium bovis / Q000276:immunology*; D018570:Risk Assessment; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma