HIV and the Post-Tuberculosis Cardiopulmonary Syndrome
One of every 50 people currently alive is a survivor of TB disease. More than half of TB survivors experience post-treatment chronic lung disease, and TB survivors carry a six-fold increased risk of pulmonary hypertension. The presentation of acute TB disease is dramatically modulated by HIV status, and HIV itself is a cause of pulmonary hypertension and accelerated chronic lung disease. These colliding epidemics are felt most heavily in sub-Saharan Africa, where 29% of TB patients are people with HIV. However, the cardiopulmonary outcomes of pulmonary TB among PWH have been primarily assessed at treatment completion, and the long term impact on chronic lung disease and persistent pulmonary hypertension are unknown. At present, there are no biomarkers or disease-specific therapies for post-TB chronic lung disease. Our study will include 90 pulmonary TB survivors (75 people with HIV and 15 HIV-uninfected adults) and 180 controls matched for HIV status, age and sex in Mwanza, Tanzania. We hypothesize that a history of pulmonary TB in Tanzania will be a driver of underdiagnosed (Aim 1) chronic lung disease as evidenced by impaired spirometry, and (Aim 2) pulmonary hypertension with right heart dysfunction as evidenced by echocardiography. We further hypothesize that chronic lung disease after pulmonary TB will be associated with persistently elevated plasma levels of Matrix Metalloproteinase-9, as demonstrated in HIV-associated lung disease and highly active COPD, thus opening the door for the use of Matrix Metalloproteinase inhibitors such as doxycycline to mitigate chronic lung disease after pulmonary TB.