The researches find that the Immune restoration on antiretroviral therapy (ART) can drive inflammation in HIV-infected patients with pulmonary tuberculosis (TB), but the effects on the lungs have not been assessed. They evaluated associations between pulmonary inflammation; recovery of pathogen-specific CD4 T cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB.
The antiretroviral therapy
Antiretroviral therapy (ART) improves survival in HIV-infected adults with pulmonary tuberculosis (TB), but ART may trigger the TB immune reconstitution inflammatory syndrome (TB-IRIS). Severe TB-IRIS; requiring hospitalization or medical procedures; occurred in approximately 40% who started ART in the initial two weeks after TB treatment initiation in a trial in South Africa. Furthermore; the effects of IRIS on involved organ function are largely unknown.
Nearly half of those with pulmonary TB have impaired lung function after cure; including either decreased forced expiratory volume in 1 second (FEV1); a measure of airflow obstruction; decreased functional vital capacity (FVC), a measure of restriction, or both. These defects likely relate to pulmonary inflammation. Although inflammation may resolve quickly after starting TB treatment; individuals with pulmonary TB and HIV may experience incident lung involvement on ART, providing an opportunity to evaluate mediators of lung damage prospectively. This is important as effects of IRIS on target organ
function are unknown.
F-fluorodeoxyglucose (FDG) PET-CT scanning can characterize and quantify pulmonary inflammation in TB. Furthermore, pulmonary enhancement on FDG PET-CT has been correlated with improved probability of microbiologic cure in adults with drug-resistant TB; indicating clinical relevance . No studies to our knowledge have used this modality to study
the relationship between lung inflammation and longer-term lung function in HIV/TB.
Animal models indicate an important role for CD4 T cells in TB granuloma and cavity formation. We therefore tested the hypothesis that greater functional CD4 T cell recovery on ART worsens pulmonary inflammation and impairs lung function in HIV/TB co-infected adults. They also evaluated the relationship between pulmonary glycolytic activity, lung function and
respiratory symptoms prior to and early after ART initiation; and correlated early changes in lung function to longer-term pulmonary impairment on ART.
CD4 T cell function
The primary findings of the present study are that 1) greater lung inflammation on FDG PET-CT is associated with worse lung function and symptoms prior to ART initiation and 2) greater recovery of pathogen-specific CD4 T cell function on ART is associated with increased pulmonary inflammation and decreased lung function in HIV-infected individuals with pulmonary TB.