title: The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation.
abstract: OBJECTIVE
  To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation.
  
  
  METHODS
  A prospective cohort study.
  
  
  METHODS
  Biomarkers were measured with multiplex assays in centralized laboratories using stored serum samples contributed by 1697 men during 8903 person-visits in the Multicenter AIDS Cohort Study (MACS) from 1984 to 2009. Using generalized gamma models, we compared biomarker values across three groups, adjusting for possible confounders: HIV-uninfected (NEG); HIV-positive, HAART-naive (NAI); and HAART-exposed with HIV RNA suppressed to less than 50 copies/ml plasma (SUP). We also estimated changes in biomarker levels associated with duration of HIV suppression, using splined generalized gamma regression with a knot at 1 year.
  
  
  RESULTS
  Most biomarkers were relatively normalized in the SUP group relative to the NAI group; however, 12 biomarkers in the SUP group were distinct (P < 0.002) from NEG values: CXCL10, C-reactive protein (CRP), sCD14, sTNFR2, tumour necrosis factor-alpha (TNF-α), sCD27, sGP130, interleukin (IL)-8, CCL13, BAFF, GM-CSF and IL-12p70. Thirteen biomarkers exhibited significant changes in the first year after viral suppression, but none changed significantly after that time.
  
  
  CONCLUSIONS
  Biomarkers of inflammation and immune activation moved towards HIV-negative levels within the first year after HAART-induced HIV suppression. Although several markers of T-cell activation returned to levels present in HIV-negative men, residual immune activation, particularly monocyte/macrophage activation, was present. This residual immune activation may represent a therapeutic target to improve the prognosis of HIV-infected individuals receiving HAART.
authors: aJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland bUCLA David Geffen School of Medicine, Los Angeles, California cUniversity of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania dNorthwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Nikolas Itaru
authors: NI
authors: Wada
authors: Lisa P
authors: LP
authors: Jacobson
authors: Joseph B
authors: JB
authors: Margolick
authors: Elizabeth Crabb
authors: EC
authors: Breen
authors: Bernard
authors: B
authors: Macatangay
authors: Sudhir
authors: S
authors: Penugonda
authors: Otoniel
authors: O
authors: Martínez-Maza
authors: Jay H
authors: JH
authors: Bream
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D019742:Chemokines, CC / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D015850:Interleukin-6; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D015415:Biomarkers; D019742:Chemokines, CC; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
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