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Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

¹ Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; ² Wellcome Trust Center for Research in Clinical Tropical Medicine and Department of Infectious Diseases Epidemiology, Wright Fleming Institute, Imperial College London, London, United Kingdom; ³ Medicins sans Frontières South Africa, Khayelitsha Site B Community Health Clinic, Khayelitsha Township, South Africa; and ⁴ School of Public Health, ⁵ Division of Pharmacology, and ⁶ Department of Medicine, University of Cape Town, Cape Town, South Africa

Correspondence and requests for reprints should be addressed to Robert J. Wilkinson, F.R.C.P., Room S2.19.4, Wernher and Beit Building South, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa. E-mail: r.j.wilkinson{at}imperial.ac.uk

Rationale: Two forms of the IFN- release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment.

Objective: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons.

Methods: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000.

Measurements and Main Results: One hundred and sixty (74 HIV⁺ and 86 HIV^–) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people ( = 0.52–0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group ( = 0.07–0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB ( = 0.18–0.24).

Interpretation: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis.

Key Words: diagnostic techniques and procedures • antigens • interferons • ESAT-6 protein • CFP-10 protein

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Tuberculosis infection may be accurately diagnosed by IFN- release assay. However, these tests have not been rigorously evaluated in settings where there is a high prevalence of HIV infection and high incidence of tuberculosis. What This Study Adds to the Field IFN- release assay sensitivity appears relatively unaffected by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair.

 

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