title: Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. The Uganda-Case Western Reserve University Research Collaboration.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA. jlj@po.cwru.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Nyole
authors.forename: A
authors.initials: A
authors.lastname: Okwera
authors.forename: C C
authors.initials: CC
authors.lastname: Whalen
authors.forename: P
authors.initials: P
authors.lastname: Nsubuga
authors.forename: V
authors.initials: V
authors.lastname: Pekovic
authors.forename: R
authors.initials: R
authors.lastname: Huebner
authors.forename: R S
authors.initials: RS
authors.lastname: Wallis
authors.forename: P N
authors.initials: PN
authors.lastname: Mugyenyi
authors.forename: R D
authors.initials: RD
authors.lastname: Mugerwa
authors.forename: J J
authors.initials: JJ
authors.lastname: Ellner
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000293:Adolescent; D000328:Adult; D000946:Antigens, Fungal / Q000276:immunology; D000995:Antitubercular Agents / Q000627:therapeutic use; D002175:Candida / Q000276:immunology*; D015331:Cohort Studies; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010919:Placebos; D011446:Prospective Studies; D015203:Reproducibility of Results; D012882:Skin Tests; D014373:Tuberculin / Q000276:immunology*; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014454:Uganda
chemical_list: D000946:Antigens, Fungal; D000995:Antitubercular Agents; D010919:Placebos; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D007538:Isoniazid