Mentored Scientist Award

CAPTURE Study: Causes and Predictors of post-Tuberculosis Restrictive lung disease in people with and without HIV in Uganda

Headshot of Katerina Byanova, MD, MS
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Award amount - Direct


Post-tuberculosis lung disease (PTLD), a heterogeneous group of abnormalities including obstructive (airway), restrictive (fibrotic), pleural, and pulmonary vascular diseases, occurs in approximately 50% of people with cured tuberculosis (TB) and is a source of significant morbidity. HIV is a known risk factor for TB and for more severe disease, but its impact on PTLD is unclear. Some reports suggest lower rates of PTLD in people living with HIV (PWH) since immunosuppression can increase extra-pulmonary dissemination and lead to less TB cavitation and parenchymal lung disease at time of TB diagnosis; others suggest an increase in PTLD related to immune reconstitution inflammatory syndromes during early antiretroviral therapy since many inflammatory pathways promote tissue destruction and remodeling. Understanding how HIV affects PTLD risk and the mechanistic underpinnings of these associations is important because it can lead to better PTLD care, management, and prevention in this vulnerable population. This project aims to understand the mechanistic pathways driving an HIV-specific difference in the prevalence of restrictive PTLD observed in the well-characterized I AM OLD-DA cohort of patients with and without HIV whose lung function is followed longitudinally after acute TB in Kampala, Uganda. Our overall hypothesis is that the kynurenine pathway of tryptophan catabolism (KP), which is more highly activated in PWH, leads to poor TB containment and disease dissemination prior to TB treatment. However, persistent KP elevation in PWH after TB treatment promotes TGF-beta activation and can lead to lung fibrosis. This project will help us develop a deeper understanding of the HIV-specific mechanisms modifying PTLD risk in this population, and it will also serve as a foundation for a K23 grant application aiming to better understand, predict, and mitigate PTLD development.