title: Associations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy.
abstract: OBJECTIVE
  One of the goals of antiretroviral therapy (ART) is to attenuate HIV-induced systemic immune activation and inflammation. We determined the dynamics of biomarkers of immune activation, microbial translocation and inflammation during initial ART with a nucleos(t)ide-sparing regimen of darunavir/ritonavir plus raltegravir. We also evaluated associations between these biomarkers and the virological response to the regimen.
  
  
  METHODS
  We determined baseline and week 24 and 48 levels of CD4+ and CD8+ T cell activation (% HLA-DR+/CD38+), interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), soluble CD14 (sCD14), D-dimer and lipopolysaccharide. Associations between the biomarkers at baseline were assessed using Spearman's rank correlation. The Wilcoxon signed rank test analysed changes from baseline. Comparisons between groups were made using the Wilcoxon rank sum test, and Cox proportional hazards models assessed predictors of virological failure (VF).
  
  
  RESULTS
  Assays were completed on 107 of 112 subjects after excluding five subjects who had only baseline samples. The subjects included were 94 (88%) men with a median age of 37 years, a median baseline CD4 count of 261.5 cells/mm(3) and a median baseline viral load (VL) of 75 876 copies/mL. Subjects with a baseline VL >100 000 copies/mL had higher baseline T cell activation, IL-6, IP-10, sCD14 and D-dimer. These biomarkers declined during treatment (P < 0.05). Although subjects who experienced VF had higher baseline CD4+ T cell activation (P = 0.035), only baseline VL independently predicted VF (hazard ratio for >100 000 versus ≤100 000 copies/mL was 4.5-5.6, P ≤ 0.002).
  
  
  CONCLUSIONS
  Darunavir/ritonavir plus raltegravir attenuated immune activation, inflammation and microbial translocation. T cell activation remained higher in subjects with VF than those without. Baseline VL >100 000 copies/mL remained the primary driver of VF.
authors.affiliation: Division of Infectious Diseases, Northwestern University, Chicago, IL 60611, USA. b-taiwo@northwestern.edu
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Peter S
authors.initials: PS
authors.lastname: Kim
authors.forename: Baiba I
authors.initials: BI
authors.lastname: Berzins
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Amy
authors.initials: A
authors.lastname: Jennings
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D000069454:Darunavir; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D011760:Pyrrolidinones; D013449:Sulfonamides; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir
keywords: microbial translocation; nucleos(t)ide sparing; soluble CD14