Impact of HIV infection on early responses to TB exposure

Tuberculosis (TB)-related morbidity and mortality remains unacceptably high among people with HIV infection and the risk of TB infection remains elevated even among people with HIV on antiretroviral therapy with normalization of their CD4 cell count. While HIV infection has been shown to impair the pulmonary immune response, the nature and impact of these impairments in the setting of TB infection have not been fully characterized. We propose to address these gaps in knowledge by characterizing the phenotypic and functional characteristics of the alveolar cellular population, which are critical to lung immunity, among people with HIV infection. Specifically, we will characterize pulmonary lymphocytes and their activation profiles as well as assess alveolar macrophage activation potential in response to stimulation with TB antigens. Study population and design: We will conduct study with prospective enrollment of 30 participants with HIV infection who have been on antiretroviral therapy for a minimum of 18 months and 30 healthy controls. Participants will be screened for study eligibility and then will undergo bronchoscopy with bronchoalveolar lavage (BAL) at Grady Memorial Hospital. Outcome measures: De-identified BAL fluid will be analyzed for the following measures: baseline cell count and differential assessment of alveolar cellular populations, lymphocyte activation profiles, and alveolar macrophage activation profiles in response to stimulation with TB antigens.