title: Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy.
abstract: OBJECTIVE
  HIV-1 replication and microbial translocation occur concomitant with systemic immune activation. This study delineates mechanisms of immune activation and CD4 T-cell decline in pediatric HIV-1 infection.
  
  
  METHODS
  Cross-sectional and longitudinal cellular and soluble plasma markers for inflammation were evaluated in 14 healthy and 33 perinatally HIV-1-infected pediatric study volunteers prior to and over 96 weeks of protease-inhibitor-containing combination antiretroviral therapy (ART). All HIV-1-infected patients reconstituted CD4 T cells either with suppression of viremia or rebound of drug-resistant virus.
  
  
  METHODS
  Systemic immune activation was determined by polychromatic flow cytometry of blood lymphocytes and ELISA for plasma soluble CD27, soluble CD14, and tumor necrosis factor. Microbial translocation was evaluated by limulus amebocyte lysate assay to detect bacterial lipopolysaccharide (LPS) and ELISA for antiendotoxin core antigen immunoglobulin M (IgM) antibodies. Immune activation markers were compared with viral load, CD4 cell percentage, and LPS by regression models. Comparisons between healthy and HIV-1-infected or between different viral outcome groups were performed by nonparametric rank sum.
  
  
  RESULTS
  Microbial translocation was detected in healthy infants but resolved with age (P < 0.05). LPS and soluble CD14 levels were elevated in all HIV-1-infected patients (P < 0.05 and P < 0.0001, respectively) and persisted even if CD4 T cells were fully reconstituted, virus optimally suppressed, and lymphocyte activation resolved by ART. Children with CD4 T-cell reconstitution but viral rebound following ART continued to display high levels of soluble CD27.
  
  
  CONCLUSIONS
  Microbial translocation in pediatric HIV-1 infection is associated with persistent monocyte/macrophage activation independent of viral replication or T-cell activation.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wallet
authors.forename: Carina A
authors.initials: CA
authors.lastname: Rodriguez
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.forename: Sara
authors.initials: S
authors.lastname: Saporta
authors.forename: Sasawan
authors.initials: S
authors.lastname: Chinratanapisit
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: John W
authors.initials: JW
authors.lastname: Sleasman
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Goodenow
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D018988:Bacterial Translocation; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
chemical_list: D018950:Lipopolysaccharide Receptors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha