title: A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy.
abstract: BACKGROUND
  Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation.
  
  
  METHODS
  HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.
  
  
  RESULTS
  Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers.
  
  
  CONCLUSIONS
  In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.
authors.forename: Ashley
authors.initials: A
authors.lastname: Canipe
authors.forename: Takondwa
authors.initials: T
authors.lastname: Chidumayo
authors.forename: Meridith
authors.initials: M
authors.lastname: Blevins
authors.forename: Michael
authors.initials: M
authors.lastname: Bestawros
authors.forename: Jay
authors.initials: J
authors.lastname: Bala
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.forename: Suzanne
authors.initials: S
authors.lastname: Filteau
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Heimburger
authors.affiliation: Vanderbilt Institute for Global Health, Nashville, TN, USA. john.r.koethe@vanderbilt.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Koethe
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018988:Bacterial Translocation; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D016867:Immunocompromised Host; D007249:Inflammation / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D044342:Malnutrition / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000097:blood; D010865:Pilot Projects; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015024:Zambia; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D019380:Anti-HIV Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D002352:Carrier Proteins; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein