Sensitivity of IFN-gamma release assay to detect latent tuberculosis infection is retained in HIV-infected patients but dependent on HIV/AIDS progression

PLoS One. 2008 Jan 16;3(1):e1441. doi: 10.1371/journal.pone.0001441.


Background: Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV.

Objective: To assess the validity of a newly developed in-house ELISPOT interferon-gamma release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST).

Methodology/principal findings: ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain.

Conclusion: Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / complications
  • AIDS-Related Opportunistic Infections / diagnosis*
  • AIDS-Related Opportunistic Infections / pathology
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon-gamma / metabolism*
  • Sensitivity and Specificity
  • Tuberculosis / complications
  • Tuberculosis / diagnosis*
  • Tuberculosis / pathology


  • Interferon-gamma