Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study

Clin Exp Immunol. 2007 Oct;150(1):91-8. doi: 10.1111/j.1365-2249.2007.03462.x. Epub 2007 Aug 3.


Tuberculosis is the most frequent co-infection in human immunodeficiency virus (HIV)-infected individuals, and which still presents diagnostic difficulties. Recently we set up an assay based on interferon (IFN)-gamma response to region of difference 1 (RD1) peptides selected by computational analysis which is associated with active Mycobacterium tuberculosis replication. The objective of this study was to investigate the response to RD1 selected peptides in HIV-1-infected individuals in a clinical setting. The mechanisms of this immune response and comparison with other immune assays were also investigated. A total of 111 HIV-infected individuals with symptoms and signs consistent with active tuberculosis were enrolled prospectively. Interferon (IFN)-gamma responses to RD1 selected peptides and recall antigens were evaluated by enzyme-linked immunospot assay. Results were correlated with CD4(+) T cell counts, individuals' characteristics, tuberculin skin test, QuantiFERON-TB Gold and T-SPOT.TB. Results from 21 (19%) individuals were indeterminate due to in vitro cell anergy. Among 'non-anergic' individuals, sensitivity for active tuberculosis of the assay based on RD1 selected peptides was 67% (24 of 36), specificity was 94% (three of 54). The assay also resulted positive in cases of extra-pulmonary and smear-negative pulmonary active tuberculosis. The response was mediated by CD4(+) effector/memory T cells and correlated with CD4(+) T cell counts, but not with plasma HIV-RNA load. Moreover, the RD1 selected peptides assay had the highest diagnostic odds ratio for active tuberculosis compared to tuberculin skin test (TST), QuantiFERON-TB Gold and T-SPOT.TB. RD1 selected peptides assay is associated with M. tuberculosis replication in HIV-infected individuals, although T cell anergy remains an important obstacle to be overcome before the test can be proposed as a diagnostic tool.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / immunology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • Clonal Anergy
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / immunology
  • Female
  • HIV Infections / complications*
  • HIV Infections / immunology
  • HIV-1*
  • Humans
  • Interferon-gamma / biosynthesis
  • Male
  • Mycobacterium tuberculosis / growth & development
  • Pilot Projects
  • Prospective Studies
  • Tuberculin Test
  • Tuberculosis / complications
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology
  • Tuberculosis / microbiology


  • Antigens, Bacterial
  • Bacterial Proteins
  • Epitopes
  • Interferon-gamma