SUBCUTANEOUS INTERFERON-GAMMA FOR TB/HIV

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是随机分配结核病（TB）患者接受重组干扰素- γ (rIFN-g) 200微克皮下注射，每周3次，持续4个月，或接受同时资助的研究的两个随机组（气溶胶干扰素或安慰剂）之一的治疗，宿主对结核病和艾滋病的反应（NIH 059832; SPID no. 5）。826)。InterMune为这项研究以及对结核病和艾滋病的宿主反应免费提供rIFN-g。由于美国国立卫生研究院资助的方案不能改变以增加第三个治疗组，因此该方案将提供额外患者到皮下治疗组的随机化，以便对皮下IFN与气溶胶和安慰剂组进行无偏比较。特别是，需要检验的假设是，给药类型（皮下给药还是气溶胶给药）是否会影响肺结核患者的免疫和纤维化功能终点。具体目的如下：1)在NIH 059832中随机分配患者接受本方案中描述的皮下IFN-g与气溶胶或安慰剂。该研究将在轻度至中度肺结核患者中进行，以评估每周3次皮下注射200 mcg rIFN-g 1b加直接观察短程治疗（DOTS） 16周的疗效。结核病患者将按2:1随机分配，即每1名患者分配2名患者到NIH方案，每1名患者到这个单独的子研究。2)评估rIFN-g治疗前后支气管肺泡灌洗细胞和pbmc，以表征Th1反应的诱导。3)通过检测TGF-b系统和肺功能基因组研究，确定与改善双侧空洞性结核病纤维化和组织破坏有关的rIFN-g的体内分子效应

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