title: Systemic immune activation and microbial translocation in dual HIV/tuberculosis-infected subjects.
abstract: BACKGROUND
  Systemic immune activation is a strong predictor of progression of human immunodeficiency virus type 1 (HIV-1) disease and a prominent feature of infection with Mycobacterium tuberculosis.
  
  
  OBJECTIVE
  To understand the role of systemic immune activation and microbial translocation in HIV/tuberculosis dually infected patients over the full spectrum of HIV-1 immunodeficiency, we studied circulating sCD14 and lipopolysaccharide (LPS) and their relationship to HIV-1 activity.
  
  
  METHODS
  Two cohorts of HIV/tuberculosis subjects defined by CD4 T-cell count at time of diagnosis of tuberculosis were studied: those with low (<350/μL) and those with high (≥ 350/μL) CD4 T-cell count. Circulating soluble CD14 (sCD14) and LPS were assessed.
  
  
  RESULTS
  Levels of sCD14 were higher in HIV/tuberculosis with high (≥ 350/μL) as compared to low CD4 T-cell count (P < .001). Whereas sCD14 levels remained elevated in HIV/tuberculosis subjects with lower CD4 T-cell counts despite treatment of tuberculosis, in HIV/tuberculosis patients with higher CD4 T-cell count (≥ 350/μL), levels declined regardless of whether highly active antiretroviral therapy (HAART) was included with the anti-tuberculosis regimen. Circulating LPS levels in HIV/tuberculosis patients with CD4 T-cell count ≥ 350/μL were unaffected by treatment of tuberculosis with or without HAART.
  
  
  CONCLUSIONS
  During HIV/tuberculosis, systemic immune activation is dissociated from microbial translocation. Changes in circulating sCD14 and LPS are dependent on CD4 T-cell count.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, USA. zxt2@case.edu
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.forename: Sohani
authors.initials: S
authors.lastname: Sirdeshmuk
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Whalen
authors.forename: Maria W
authors.initials: MW
authors.lastname: Nanteza
authors.forename: Denise F
authors.initials: DF
authors.lastname: Johnson
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Christina S
authors.initials: CS
authors.lastname: Hirsch
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use; D018988:Bacterial Translocation; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000382:microbiology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D014454:Uganda; D019562:Viral Load
chemical_list: D000995:Antitubercular Agents; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides
keywords: HIV-1; LPS; soluble CD14; tuberculosis