Interferon γ responses to mycobacterial antigens protect against subsequent HIV-associated tuberculosis.

Abstract

BACKGROUND:

The cellular immune responses that protect against tuberculosis have not been identified.

METHODS:

We assessed baseline interferon γ (IFN‐γ) and lymphocyte proliferation assay (LPA) responses to antigen 85 (Ag85), early secretory antigenic target 6 (ESAT‐6), and Mycobacterium tuberculosis whole cell lysate (WCL) in human immunodeficiency virus (HIV)-infected and bacille Calmette‐Guérin (BCG)-immunized adults with CD4 cell counts of >or= 200 cells/μL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania. Subjects were followed prospectively to diagnose definite or probable tuberculosis.

RESULTS:

Tuberculosis was diagnosed in 92 of 979 subjects during a mean follow‐up of 3.2 years. The relative risk of tuberculosis among subjects with positive IFN‐γ responses to Ag85 was 0.51 (95% confidence interval [CI], 0.26-0.99; P = .049), to ESAT‐6 was 0.44 (95% CI, 0.23-0.85; P = .004), and to WCL was 0.67 (95% CI, 0.49-0.88; P = .002). The relative risk of tuberculosis was not significantly associated with baseline LPA responses. In a multivariate Cox regression model, subjects with IFN‐γ responses to ESAT‐6 and WCL had a lower hazard of developing tuberculosis, with a hazard ratio for ESAT‐6 of 0.35 (95% CI, 0.16–0.77; P = .009) and a hazard ratio for WCL of 0.30 (95% CI, 0.16-0.56; P < .001).

CONCLUSIONS:

Baseline IFN‐γ responses to ESAT-6 and WCL were associated with protection from subsequent tuberculosis among HIV-infected subjects with childhood BCG immunization in a region of high tuberculosis prevalence. Trial registration. ClinicalTrials.gov identifier: NCT00052195.

• Authors: Timothy Lahey, Siddharth Sheth, Mecky Matee, Robert Arbeit, C Robert Horsburgh, Lillian Mtei, Todd Mackenzie, Muhammad Bakari, Jenni M Vuola, Kisali Pallangyo, C Fordham von Reyn
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 202 Issue 8 Pg. 1265-72 (Oct 15 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20812851 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• BCG Vaccine
• Interferon-gamma

Topics

• Adult
• Antigens, Bacterial (immunology)
• BCG Vaccine (immunology)
• CD4 Lymphocyte Count
• Female
• HIV Infections (complications, immunology)
• Humans
• Interferon-gamma (blood, immunology)
• Male
• Mycobacterium tuberculosis (immunology)
• Risk Factors
• Tanzania
• Tuberculosis (complications, immunology)