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Polyantigenic interferon-γ responses are associated with protection from TB among HIV-infected adults with childhood BCG immunization.

Lahey T, Mitchell BK, Arbeit RD, Sheth S, Matee M, Horsburgh CR, MacKenzie T, Mtei L, Bakari M, Vuola JM, Pallangyo K, von Reyn CF - PLoS ONE (2011)

Bottom Line: Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB.In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001).Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB.

View Article: PubMed Central - PubMed

Affiliation: Dartmouth Medical School, Lebanon, New Hampshire, United States of America. Timothy.Lahey@Dartmouth.edu

ABSTRACT

Background: Surrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified.

Methods: HIV-infected adults with childhood BCG immunization entering the placebo arm of the DarDar TB vaccine trial in Dar es Salaam, Tanzania, were assessed for interferon gamma (IFN-γ) responses to three mycobacterial antigen preparations--secreted Mycobacterium tuberculosis antigens 85 (Ag85), early secretory antigenic target 6 (ESAT-6) and polyantigenic whole cell lysate (WCL). We investigated the association between the number of detectable IFN-γ responses at baseline and the subsequent risk of HIV-associated TB.

Results: During a median follow-up of 3.3 years, 92 (9.4%) of 979 placebo recipients developed TB. The incidence of TB was 14% in subjects with no detectable baseline IFN-γ responses vs. 8% in subjects with response to polyantigenic WCL (P = 0.028). Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB. Overall the percentage of subjects with 0, 1, 2 and 3 baseline IFN-γ responses to mycobacterial preparations who developed HIV-associated TB was 14%, 8%, 7% and 4%, respectively (P = 0.004). In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001).

Conclusions: Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB.

Trial registration: ClinicalTrials.gov NCT0052195.

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Related in: MedlinePlus

Study CONSORT diagram.ESAT-6, early secreted antigenic target 6; f/u, follow up; IFN, interferon gamma; PHA, phytohemagglutinin positive control; TB, tuberculosis.
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pone-0022074-g001: Study CONSORT diagram.ESAT-6, early secreted antigenic target 6; f/u, follow up; IFN, interferon gamma; PHA, phytohemagglutinin positive control; TB, tuberculosis.

Mentions: Among the 979 HIV-infected placebo subjects in this study, all had a BCG scar and a baseline CD4 count ≥200/mm3 at study entry. We diagnosed 92 causes of definite and probable TB during a median follow-up of 3.3 years. As we showed previously [28], subjects who developed HIV-associated TB had lower CD4 counts, had higher HIV viral loads, were more likely to have a positive TST, and were more likely to have been treated for TB previously. Figure 1 depicts the study CONSORT diagram.


Polyantigenic interferon-γ responses are associated with protection from TB among HIV-infected adults with childhood BCG immunization.

Lahey T, Mitchell BK, Arbeit RD, Sheth S, Matee M, Horsburgh CR, MacKenzie T, Mtei L, Bakari M, Vuola JM, Pallangyo K, von Reyn CF - PLoS ONE (2011)

Study CONSORT diagram.ESAT-6, early secreted antigenic target 6; f/u, follow up; IFN, interferon gamma; PHA, phytohemagglutinin positive control; TB, tuberculosis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140474&req=5

pone-0022074-g001: Study CONSORT diagram.ESAT-6, early secreted antigenic target 6; f/u, follow up; IFN, interferon gamma; PHA, phytohemagglutinin positive control; TB, tuberculosis.
Mentions: Among the 979 HIV-infected placebo subjects in this study, all had a BCG scar and a baseline CD4 count ≥200/mm3 at study entry. We diagnosed 92 causes of definite and probable TB during a median follow-up of 3.3 years. As we showed previously [28], subjects who developed HIV-associated TB had lower CD4 counts, had higher HIV viral loads, were more likely to have a positive TST, and were more likely to have been treated for TB previously. Figure 1 depicts the study CONSORT diagram.

Bottom Line: Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB.In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001).Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB.

View Article: PubMed Central - PubMed

Affiliation: Dartmouth Medical School, Lebanon, New Hampshire, United States of America. Timothy.Lahey@Dartmouth.edu

ABSTRACT

Background: Surrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified.

Methods: HIV-infected adults with childhood BCG immunization entering the placebo arm of the DarDar TB vaccine trial in Dar es Salaam, Tanzania, were assessed for interferon gamma (IFN-γ) responses to three mycobacterial antigen preparations--secreted Mycobacterium tuberculosis antigens 85 (Ag85), early secretory antigenic target 6 (ESAT-6) and polyantigenic whole cell lysate (WCL). We investigated the association between the number of detectable IFN-γ responses at baseline and the subsequent risk of HIV-associated TB.

Results: During a median follow-up of 3.3 years, 92 (9.4%) of 979 placebo recipients developed TB. The incidence of TB was 14% in subjects with no detectable baseline IFN-γ responses vs. 8% in subjects with response to polyantigenic WCL (P = 0.028). Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB. Overall the percentage of subjects with 0, 1, 2 and 3 baseline IFN-γ responses to mycobacterial preparations who developed HIV-associated TB was 14%, 8%, 7% and 4%, respectively (P = 0.004). In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001).

Conclusions: Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB.

Trial registration: ClinicalTrials.gov NCT0052195.

Show MeSH
Related in: MedlinePlus