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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

Survival without HIV-associated tuberculosis (TB) according to number of baseline interferon gamma (IFN-γ) responses detected against mycobacterial preparations.The hazard of HIV-associated TB fell 46% with each increment in the number of detectable baseline IFN-γ responses against mycobacterial preparations. HR, hazard ratio; TB, tuberculosis.
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pone-0022074-g003: Survival without HIV-associated tuberculosis (TB) according to number of baseline interferon gamma (IFN-γ) responses detected against mycobacterial preparations.The hazard of HIV-associated TB fell 46% with each increment in the number of detectable baseline IFN-γ responses against mycobacterial preparations. HR, hazard ratio; TB, tuberculosis.

Mentions: We used a multivariate Cox regression model to assess the hazard of developing HIV-associated TB relative to the number of detectable baseline IFN-γ responses against mycobacterial antigen preparations. In unadjusted analyses, the hazard decreased significantly with each incremental increase in the number of baseline IFN-γ responses (hazard ratio [HR] 0.62, 95% confidence intervals [CI] 0.47-0.81, P = 0.001). This relationship remained significant after adjusting for age, baseline CD4 count, previous TB treatment and a positive TST (HR 0.54, 95% CI 0.38–0.75, P<0.001; Figure 3). Compared to subjects with baseline IFN-γ responses to WCL alone, subjects responding to both WCL and ESAT-6 exhibited a trend toward enhanced protection from HIV-associated TB compared (HR 0.43, 95% CI 0.18−1.06, P = 0.069), whereas subjects responding to both WCL and Ag85 did not (HR 0.85, 95% CI 0.35−2.05, P = 0.715).


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)

Survival without HIV-associated tuberculosis (TB) according to number of baseline interferon gamma (IFN-γ) responses detected against mycobacterial preparations.The hazard of HIV-associated TB fell 46% with each increment in the number of detectable baseline IFN-γ responses against mycobacterial preparations. HR, hazard ratio; TB, tuberculosis.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0022074-g003: Survival without HIV-associated tuberculosis (TB) according to number of baseline interferon gamma (IFN-γ) responses detected against mycobacterial preparations.The hazard of HIV-associated TB fell 46% with each increment in the number of detectable baseline IFN-γ responses against mycobacterial preparations. HR, hazard ratio; TB, tuberculosis.
Mentions: We used a multivariate Cox regression model to assess the hazard of developing HIV-associated TB relative to the number of detectable baseline IFN-γ responses against mycobacterial antigen preparations. In unadjusted analyses, the hazard decreased significantly with each incremental increase in the number of baseline IFN-γ responses (hazard ratio [HR] 0.62, 95% confidence intervals [CI] 0.47-0.81, P = 0.001). This relationship remained significant after adjusting for age, baseline CD4 count, previous TB treatment and a positive TST (HR 0.54, 95% CI 0.38–0.75, P<0.001; Figure 3). Compared to subjects with baseline IFN-γ responses to WCL alone, subjects responding to both WCL and ESAT-6 exhibited a trend toward enhanced protection from HIV-associated TB compared (HR 0.43, 95% CI 0.18−1.06, P = 0.069), whereas subjects responding to both WCL and Ag85 did not (HR 0.85, 95% CI 0.35−2.05, P = 0.715).

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