Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. The Uganda-Case Western Reserve University Research Collaboration

Am J Respir Crit Care Med. 1998 Dec;158(6):1790-6. doi: 10.1164/ajrccm.158.6.9803104.


Anergy testing has been used as an adjunct to tuberculin testing for assessing M. tuberculosis (MTB) infection and indications for isoniazid preventive therapy in HIV-infected persons. We examined factors associated with the stability of skin test responses to purified protein derivative (PPD) and candida antigens in a cohort of HIV-infected adults followed prospectively in a tuberculosis preventive therapy trial in Uganda. PPD-positive and anergic subjects in the placebo arms of the preventive therapy study underwent repeat skin testing and immunologic testing including measurement of MTB culture filtrate (CF)-stimulated interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels in whole-blood culture supernatants. Anergy was present in 27% of 4,058 HIV-infected subjects screened for the tuberculosis preventive therapy trial compared with 10% of 682 HIV-non-infected persons. On follow-up testing of enrolled subjects, 42% of 139 initially anergic subjects were no longer anergic; two thirds of these had PPD reactions >= 5 mm. Stability of anergy was associated with intercurrent opportunistic infections and AIDS-associated dermatitis at baseline. Thirty-five percent of 313 subjects with an initial positive PPD had a negative PPD test at follow-up, 26% of whom had a positive candida skin test at the same time as the negative PPD test. Baseline MTBCF-stimulated IFN-gamma levels were significantly higher among PPD-positive subjects who remained PPD-positive than in those who were falsely negative. We conclude first that anergy is unstable and second that anergy testing is unreliable in identifying HIV-infected adults who are not infected with MTB and should not be used routinely for this purpose in assessing indications for isoniazid preventive therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / prevention & control
  • Adolescent
  • Adult
  • Antigens, Fungal / immunology
  • Antitubercular Agents / therapeutic use
  • Candida / immunology*
  • Cohort Studies
  • False Negative Reactions
  • Female
  • Follow-Up Studies
  • HIV Infections / immunology*
  • Humans
  • Interferon-gamma / blood
  • Isoniazid / therapeutic use
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Placebos
  • Prospective Studies
  • Reproducibility of Results
  • Skin Tests
  • Tuberculin / immunology*
  • Tuberculin Test
  • Tuberculosis, Pulmonary / prevention & control
  • Tumor Necrosis Factor-alpha / analysis
  • Uganda


  • Antigens, Fungal
  • Antitubercular Agents
  • Placebos
  • Tuberculin
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Isoniazid