title: Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa.
abstract: BACKGROUND
  Interferon-gamma (IFN-gamma) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates.
  
  
  METHODS
  IFN-gamma responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done.
  
  
  RESULTS
  ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/mul compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10-0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls.
  
  
  CONCLUSIONS
  The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation.
authors.affiliation: The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. stevelawn@yahoo.co.uk
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Nonzwakazi
authors.initials: N
authors.lastname: Bangani
authors.forename: Monica
authors.initials: M
authors.lastname: Vogt
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Motasim
authors.initials: M
authors.lastname: Badri
authors.forename: Marjorie
authors.initials: M
authors.lastname: Ntobongwana
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D011933:Reagent Kits, Diagnostic; D007371:Interferon-gamma