Clinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected Africans

Background. Human immunodeficiency virus (HIV)-associated tuberculosis is a major cause of mortality in Africa. The assay of T cell interferon-gamma released in response to antigens of greater specificity than purified protein derivative is a useful improvement over the Mantoux tuberculin skin test, but few studies have evaluated interferon gamma secretion in HIV-infected individuals. Methods. Mycobacterium tuberculosis antigen-specific interferon-gamma secretion was assessed by whole blood assay and enzyme-linked immunospot, which were compared with the Mantoux tuberculin skin test in HIV-infected and HIV-uninfected individuals without active tuberculosis and HIV-infected patients with pulmonary tuberculosis in Khayelitsha, South Africa. Results. The skin test and whole blood assay responses to purified protein derivative in HIV-positive subjects were decreased, compared with responses in HIV-negative subjects (P < .001). By contrast, the responses to M. tuberculosis antigens (early secreted antigenic target 6, culture filtrate protein 10, TB10.3, and alpha-crystallin 2) were less affected, indicating a high prevalence of latent tuberculosis (similar to 80%) in both HIV-negative and HIV-positive subject groups. Whole blood assay responses did not differ between the HIV-positive subjects without tuberculosis and HIV-positive subjects with tuberculosis, but the enzyme-linked immunospot method response to early secreted antigenic target 6 and culture filtrate protein 10 was higher in the group of HIV-infected subjects with tuberculosis (P <= .04), although this group had lower CD4(+) cell counts. A ratio of the combined enzyme-linked immunospot method response divided by the CD4(+) cell count of 11.0 had 88% sensitivity and 80% specificity for active pulmonary tuberculosis in HIV-infected individuals. Conclusions. Interferon-gamma release appears to be less impaired than skin testing by HIV coinfection. The novel potential to relate the enzyme-linked immunospot method and CD4(+) cell count to assist diagnosis of active tuberculosis in patients with HIV infection is important and deserves further evaluation.