Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1790-1796

Instability of Tuberculin and Candida Skin Test Reactivity in HIV-infected Ugandans

JOHN L. JOHNSON, SAM NYOLE, ALPHONSE OKWERA, CHRISTOPHER C. WHALEN, PETER NSUBUGA, VUKOSAVA PEKOVIC, ROBIN HUEBNER, ROBERT S. WALLIS, PETER N. MUGYENYI, ROY D. MUGERWA, and JERROLD J. ELLNER, for the Uganda-Case Western Reserve University Research Collaboration

Department of Medicine, Division of Infectious Diseases, and Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio; National TB and Leprosy Control Programme, Joint Clinical Research Center, and Department of Medicine, Mulago Hospital and Makerere University, Kampala, Uganda; Centers for Disease Control and Prevention, Atlanta, Georgia.

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-) and tumor necrosis factor alpha (TNF-) 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- 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.

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