title: Asymptomatic HIV-infected individuals on antiretroviral therapy exhibit impaired lung CD4(+) T-cell responses to mycobacteria.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Malawi-Liverpool-Wellcome Trust Clinical Research Programme and.
authors.forename: Kondwani C
authors.initials: KC
authors.lastname: Jambo
authors.forename: Dominic H
authors.initials: DH
authors.lastname: Banda
authors.forename: Louise
authors.initials: L
authors.lastname: Afran
authors.forename: Anstead M
authors.initials: AM
authors.lastname: Kankwatira
authors.forename: Rose D
authors.initials: RD
authors.lastname: Malamba
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Allain
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: David G
authors.initials: DG
authors.lastname: Russell
authors.forename: Henry C
authors.initials: HC
authors.lastname: Mwandumba
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D058345:Asymptomatic Infections; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000209:etiology*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: ART; HIV; Mycobacterium tuberculosis; T cells; macrophages