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.
This HIV Research Training Program will help to build sustainable research capacity in Post Graduate Institute of Medical Education and Research in India by enhancing the scientific expertise of investigators in performing research that will address the challenges created by dual epidemics of HIV and TB. The goal is to provide training and capacity building for fostering basic research on understanding the pathogenesis of pulmonary and extrapulmonary TB, especially in HIV+ patients, with the ultimate goal of devising rapid, simple and accurate point-of-care methods for diagnosis of active and subclinical, pulmonary and extrapulmonary TB Immigrants from TB-endemic countries continue to be the major population subset that is diagnosed with TB in the US. The project is also highly relevant to the public health of the United States and its citizens.