Immunopathogenesis and diagnosis of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome during early antiretroviral therapy

J Infect Dis. 2009 Dec 1;200(11):1736-45. doi: 10.1086/644784.


Background: In many settings, the benefits of antiretroviral therapy (ART) are reduced by the high early incidence of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS).

Methods: We used tuberculin skin testing and the QuantiFERON-TB Gold In-Tube assay to investigate cellular immune responses to purified protein derivative (PPD) and region of difference 1 (RD1) antigens during the first 24 weeks of ART.

Results: TB-IRIS and ART-associated tuberculosis occurred in 15 of 75 (20%) and 11 of 231 (4.8%) participants at risk, respectively. Greater increases in interferon gamma (IFN-gamma) and skin test responses to PPD were seen at week 24 and 12 in participants with TB-IRIS (P< or = .04), respectively. Raw IFN-gamma responses to RD1 antigens and PPD corrected for pre-ART CD4(+) T cell counts were higher at all time points in individuals with ART-associated tuberculosis (P<.001) and were associated with areas under receiver operator characteristic curves of 0.90 for RD1 (95% confidence interval [CI], 0.78-1.00) and 0.92 for PPD (95% CI, 0.83-1.00) for the diagnosis of ART-associated tuberculosis. Pre-ART IFN-gamma responses enabled stratification of participants into groups with risks of subsequent tuberculosis of 0.7%, 9.3%, and 30.0%.

Conclusions: Type 1 effector T cell responses are prominent in ART-associated tuberculosis, but additional immune defects may be more important in paradoxical TB-IRIS. IFN-gamma release assays may contribute to the prediction and diagnosis of tuberculosis during early ART.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / adverse effects
  • Anti-Retroviral Agents / therapeutic use*
  • Antigens, Bacterial / immunology
  • Antitubercular Agents / therapeutic use
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / microbiology
  • HIV-1
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / diagnosis*
  • Immune Reconstitution Inflammatory Syndrome / etiology
  • Immune Reconstitution Inflammatory Syndrome / immunology*
  • Interferon-gamma / metabolism
  • Male
  • ROC Curve
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tuberculosis / drug therapy
  • Tuberculosis / immunology*


  • Anti-Retroviral Agents
  • Antigens, Bacterial
  • Antitubercular Agents
  • Interferon-gamma