Polyantigenic Interferon-c Responses Are Associated with Protection from TB among HIV-Infected Adults with Childhood BCG Immunization

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-c) 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-c 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-c 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-c responses to mycobacterial preparations who developed HIVassociated TB was 14%, 8%, 7% and 4%, respectively (P = 0.004). In amultivariate Cox regressionmodel, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-c responses (P,0.001). Conclusions: Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-c responses are associated with decreased risk of subsequent HIV-associated TB.