SUBCUTANEOUS INTERFERON-GAMMA FOR TB/HIV

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to randomize tuberculosis (TB) patients to receive recombinant interferon-gamma (rIFN-g) 200 micrograms subcutaneously 3 times a week for 4 months on this protocol or to receive treatment on one of the two randomized arms (aerosol IFN or placebo) of the concurrent funded study, Host Response to TB and AIDS (NIH 059832; SPID no. 826). InterMune is providing the rIFN-g free of charge for this study as well as for Host Response to TB and AIDS. Because the NIH-funded protocol cannot be altered to add a third treatment arm, this protocol will provide the randomization of the additional patients to the subcutaneous arm to enable an unbiased comparison of the subcutaneous IFN to the aerosol and placebo arm. In particular, the hypothesis to be tested is whether type of administration (subcutaneous vs. aerosol) affects the endpoints of immune and fibrotic functions in pulmonary TB. The specific aims are as follows: 1) Randomize patients to receive subcutaneous IFN-g as described in this protocol vs. aerosol or placebo in NIH 059832. This study will be conducted in minimal to moderate pulmonary TB patients to evaluate the efficacy of 16 weeks of 200 mcg rIFN-g 1b by subcutaneous injection three times a week plus Directly Observed Therapy Short Course (DOTS). TB patients will be allocated in a 2:1 randomization that allocates 2 patients to the NIH protocol for every 1 patient to this separate substudy. 2) Evaluate bronchoalveolar lavage cells and PBMCs before and after rIFN-g treatment to characterize the induction of a Th1 response. 3) Determine the in vivo molecular effects of rIFN-g that relate to amelioration of fibrosis and tissue destruction in bilateral, cavitary TB by examining the TGF-b system and pulmonary functional genomic studies