Abstract
RATIONALE: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4(+) T-cell responses observed in HIV-infected ART-naive adults. OBJECTIVES: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4(+) T-cell responses to Mycobacterium in HIV-infected individuals. METHODS: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4(+) T-cell responses were measured by intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4(+) T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4(+) T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4(+) T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4(+) T-cell responses were impaired in adults on ART irrespective of duration. CONCLUSIONS: AM and mycobacteria-specific alveolar CD4(+) T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated.