Lung Inflammation and Fibrosis for Targeted Intervention to Modulate Early lung dysfunction in HIV infected: LIFE TIME study

HIV infection is associated with chronic inflammation. Antiretroviral therapy
ameliorates the inflammation, however it remains high compared to non-HIV infected individuals
even when viral replication is suppressed. The chronic low grade inflammation leads to organ
dysfunction, with recent evidence indicating that lung functional decline is accelerated in treated
HIV, even after control for smoking. Most of the studies show higher rates of obstructive lung
diseases including doubling of COPD prevalence and higher rates of asthma. The link between
fibrosis and inflammation is well supported in the literature, even outside of HIV, with cytokines
such as IL6 underpinning the onset of fibrosis. Prior studies have documented that HIV infected
individuals on effective antiretroviral therapy have increases in collagen deposition in intestinal and
lymphatic tissue compared to HIV-uninfected controls. We found markers of inflammation, tissue
damage and fibrosis among HIV infected individuals with pneumonia, that individuals infected with
MTB and PJP had the most severe lung dysfunction and that lung dysfunction involved small
airways restrictive patterns. We therefore hypothesize that: Lung inflammation, injury and
fibrosis are central, modifiable causes of progressive pulmonary dysfunction in HIV.
Inflammation during pneumonia results in increased tissue damage and accelerated lung
fibrosis leading to progressive loss of lung function.