We propose that the early events in the pathogenesis of the accelerated development of COPD in smokers with HIV infection results from the premature biologic aging of the small airway epithelium (SAE) mediated by the effects of direct HIV infection of the SAE and/or through the interaction of HIV-infected T cells and/or alveolar macrophages (AM) with the SAE, resulting in the disordered biology of the SAE that is central to the pathogenesis of COPD.