In the context of improved survival from HIV infection itself, chronic obstructive pulmonary
disease (COPD); a form of lung disease that includes emphysema, which makes breathing
difficult) is emerging as an important cause of morbidity and perhaps ultimately mortality in
this population. HIV-infected patients are at increased risk of chronic obstructive pulmonary
disease, likely due to multiple factors, including an increased presence of smoking, chronic
inflammation and progression of immunodeficiency, oxidant stress (excessive levels of natural
chemicals called oxidants and free radicals that can damage tissue), and respiratory
infections. While natural history data on COPD are limited in the era of potent
antiretroviral therapy, earlier data suggest that the course of emphysema may be accelerated
in this population. Our preliminary data suggest that several matrix metalloproteinases
(MMPs) derived from alveolar macrophages (a type of immune cell found in the lungs) have an
increased cellular response in HIV-infected smokers, which could contribute to accelerated
emphysema. Matrix metalloproteinases are enzymes that break down the structural support of
tissues, including the airways in the lung.
Based on these observations, the investigators hypothesize that pharmacologic inhibition of
matrix metalloproteinases by doxycycline will favorably modify the natural history of chronic
obstructive pulmonary disease in HIV-infected patients. To test this hypothesis, the
investigators propose conducting a proof of concept pilot study as a prelude to a possible
phase II randomized, placebo-controlled trial (testing safety and efficacy in a larger
population controlled with a "sugar pill") of doxycycline for COPD in HIV-infected patients
should the proof of concept be successful. Our research team is lead by a
pulmonologist/researcher with expertise in HIV-associated COPD and an infectious diseases
specialist/clinical trials expert.