Background: Despite the high prevalence of respiratory symptoms and obstructive lung disease in HIV-infected subjects, the prevalence of bronchodilator reversibility (BDR) and asthma has not been systematically studied during the era of combination antiretroviral therapy (ART). Objective: We sought to determine the prevalence of asthma diagnosis and related pulmonary function abnormalities in an HIV-infected cohort and to identify potential mechanisms. Methods: We performed a cross-sectional analysis of 223 HIV-infected subjects with data on respiratory symptoms and diagnoses, pulmonary function, sputum cell counts, and asthma-related cytokines and chemokines in serum/sputum. Results: Doctor-diagnosed asthma was present in 46 (20.6%), and BDR (≥200 mL and ≥12% increase in FEV1 or forced vital capacity) was present in 20 (9.0%) participants. Pulmonary symptoms and function were worse in those with doctor-diagnosed asthma. Doctor-diagnosed asthma was independently associated with female sex (P =.04), body mass index of greater than 29.6 kg/m2 (vs <29.6 kg/m2, P =.03), history of bacterial or Pneumocystis pneumonia (P =.01), and not currently taking ART (P =.04) and in univariate analysis with parental history of asthma (n = 180, P =.004). High sputum eosinophil percentages (>2.3% based on the highest decile) were more likely in those with doctor-diagnosed asthma (P =.02) or BDR (P =.02). Doctor-diagnosed asthma tended to be more common with high sputum IL-4 (P =.02) and RANTES (P =.02) levels, whereas BDR was associated with high plasma macrophage inflammatory protein 1α (P =.002) and sputum macrophage inflammatory protein 1β (P =.001) levels. Conclusion: Asthma diagnosis and BDR are prevalent in an HIV-infected outpatient cohort, and associations with family history, obesity, allergic inflammation, prior infection, absence of ART, and increased HIV-stimulated cytokines suggest possible mechanisms of HIV-associated asthma. © 2011 American Academy of Allergy, Asthma & Immunology.