title: Effect of highly active antiretroviral therapy on biomarkers of B-lymphocyte activation and inflammation.
abstract: OBJECTIVE
  Chronic inflammation and B-cell hyperactivation are seen in HIV infection, contributing to an increased risk for the accrual of genetic errors that may result in B-cell lymphoma. The primary objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) on serum levels of molecules that are associated with immune activation and/or inflammation, including several that are associated with B-cell activation, specifically IL-6, sCD30, sCD27, IgG, IgA, CXCL13 (B lymphocyte chemoattractant, BLC), a B-lymphocyte chemokine involved in B-cell trafficking, as well as C-reactive protein, an acute-phase protein.
  
  
  METHODS
  We used a retrospective cohort study design, measuring serum levels of these markers at each of four 1-year intervals, 2 years before and 2 years after HAART initiation, in a subgroup of 290 HIV-infected men enrolled in the Multicenter AIDS Cohort Study (MACS).
  
  
  METHODS
  Serum levels of immune activation-associated molecules were measured by ELISA and multiplexed immunometric assays. Reference values were determined by the 5th to 95th percentiles from a sample of 109 HIV-uninfected MACS men.
  
  
  RESULTS
  HAART use was associated with a reduction, but not normalization, of most biomarkers tested. Serum levels of IL-6 and C-reactive protein appeared to be unaffected by HAART.
  
  
  CONCLUSIONS
  These results suggest a partial normalization of serum cytokine levels post HAART. However, a chronic state of B-cell hyperactivation continues 2-3 years after HAART initiation. These findings may explain, in part, the excess incidence of lymphoma still occurring in HIV-infected persons in the post-HAART era.
authors.affiliation: Department of Epidemiology, UCLA School of Public Health, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Regidor
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Breen
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Widney
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Frank
authors.initials: F
authors.lastname: Palella
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000235:genetics / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D019562:Viral Load
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein