Research Training on Pathogenesis and Diagnosis of HIV-TB

描述（由申请人提供）：印度是世界上HIV和结核分枝杆菌合并感染人数最多的国家，结核病是印度HIV+患者发病和死亡的最重要原因。hiv感染引起的免疫功能障碍改变了结核病的临床和影像学表现；HIV+结核患者通常无症状，约一半患者为少菌性，超过50%的患者为肺外结核。艾滋病毒阳性患者的少杆菌性肺结核和肺外结核难以诊断，原因是缺乏负担得起的诊断测试，往往难以获得必须进行检测的标本，以及获取用于诊断的标本所需的侵入性技术。在印度等结核病流行地区，目前用于结核病诊断的不敏感诊断测试表现不佳，导致结核病进展迅速且往往致命的人群严重漏诊。因此，尽管现有药物完全可以治疗，但由于缺乏适当的诊断工具，导致不到一半的艾滋病毒+结核病患者在死亡前得到诊断。这项艾滋病研究培训计划（HRTP）的目标是提供培训和能力建设，以促进对艾滋病毒阳性患者肺结核和肺外结核发病机制的基础研究，最终目标是设计出快速、简单和准确的即时检测方法，用于诊断活动性和亚临床、肺结核和各种形式的肺外结核。促进新的研究工作，旨在了解HIV+患者肺结核和肺外结核的发病机制、免疫反应和宿主-病原体相互作用（目标1）；提供特定细胞、分子和免疫学技术和相关故障排除方面的培训，以及启动目标1（目标2）中定义的研究项目所需的生物信息学方面的培训；指导和支持受训者在他们的母实验室发展研究项目（目标3），并在纽约大学和伙伴研究所的科学家之间建立长期合作关系（目标4）。将向印度昌迪加尔医学教育与研究研究生院（PGIMER）的年轻终身教职员工和博士生提供培训。PGIMER是纽约大学艾滋病国际培训与研究项目（AITRP，自2001年起，NCE至2014年）的七个合作机构之一。在前AITRP下培训了10名（9名教员和1名博士生），结果是：1)培训了5名临床医生，对艾滋病毒/结核病和结核病患者进行临床护理；ii)建立一个免疫缺陷诊所，为艾滋病毒阳性患者提供临床护理，该诊所现在被指定为艾滋病毒阳性患者临床管理卓越中心，并向印度北部6个邦的4000名患者提供抗逆转录病毒治疗；iii)培训3名临床分枝杆菌学家，他们现在在经认可的结核病实验室进行培养和药敏试验；iv)培训两名正在进行或已启动合作研究的基础科学教员。PGIMER正在迅速改善其研究基础设施和人员。拟议的艾滋病毒研究培训计划建议在过去十年中已经建立的这一坚实基础上继续发展。

DESCRIPTION (provided by applicant): India has the largest number of individuals co-infected with HIV and M. tuberculosis in the world, and TB is the most important cause of morbidity and mortality in HIV+ patients in India. The immune dysfunction caused by HIV-infection alters clinical and radiological presentation of TB; HIV+ TB patients are often asymptomatic, about half the patients are paucibacillary, and over 50% of the patients have extrapulmonary TB. Paucibacillary pulmonary and extrapulmonary TB in HIV+ patients is difficult to diagnose due to lack of affordable diagnostic tests, often poor accessibility to the ste from which the specimen has to be obtained for testing, and the invasive techniques required to obtain the specimen for diagnosis. The poor performance of insensitive diagnostic tests currently used for TB diagnosis in TB-endemic settings like India leads to significant under- diagnosis of TB in the very population where TB progression is rapid and often fatal. Thus, despite being totally treatable with the existing drugs, the lack of appropriate diagnostic tools results in identification of less than half of the HIV+ TB patients being diagnosed before death. The goal of this HIV Research Training Program (HRTP) is to provide training and capacity building for fostering basic research on understanding the pathogenesis of pulmonary and extrapulmonary TB in HIV+ patients, with the ultimate goal of devising rapid, simple and accurate point-of-care tests for diagnosis of active and subclinical, pulmonary and various forms of extrapulmonary TB. Facilitate new research efforts aimed at understanding the pathogenesis, immune responses and host-pathogen interaction in pulmonary and extrapulmonary TB in HIV+ patients (Aim 1); provide training in specific cellular, molecular and immunological techniques and the related troubleshooting, and in bioinformatics required for initiating the research project defined in aim 1 (Aim 2); mentor and support trainees for developing research projects in their parent lab (Aim 3), and establish long-term collaborative relationships between NYU and scientists in the partner institute (Aim 4). Training will be provided to young tenured faculty members and PhD students from the Post Graduate Institute for Medical Education and Research (PGIMER), Chandigarh, India. PGIMER was one of the seven collaborating institutions on the NYU AIDS International Training and Research Program (AITRP, since 2001; NCE till 2014). The training of 10 (9 faculty and one PhD student) under the former AITRP has resulted in i) training to 5 clinicians in clinical care of HIV/TB and TB patients; ii) establishmet of an immunodeficiency clinic for providing clinical care to HIV+ patients, that is now designated as Center of Excellence for Clinical management of HIV+ patients, and provides ART to >4000 patients from 6 states in northern India; iii) training of 3 clinical mycobacteriologists who now rn accredited TB labs for culture and drug susceptibility testing, and iv) trained two basic science faculty with whom collaborative research has been ongoing or initiated. PGIMER is rapidly improving its research infrastructure and staff. The proposed HIV Research Training Program proposes to build on this already strong foundation that has been established over the last decade.