title: Soluble biomarkers of immune activation and inflammation in HIV infection: impact of 2 years of effective first-line combination antiretroviral therapy.
abstract: OBJECTIVE
  The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation.
  
  
  METHODS
  In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression.
  
  
  RESULTS
  We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P < 0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no longer elevated in > 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 10(6)  pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART.
  
  
  CONCLUSIONS
  The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Hattab
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Guiguet
authors.affiliation: UMR_S 1135, CIMI, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1135, CIMI, Sorbonne Universities, Paris, France.|Immunology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Carcelain
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France.|Virology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Fourati
authors.affiliation: UMR_S 1135, CIMI, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1135, CIMI, Sorbonne Universities, Paris, France.|Immunology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Guihot
authors.affiliation: UMR_S 1135, CIMI, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1135, CIMI, Sorbonne Universities, Paris, France.|Immunology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Autran
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|Pitié-Salpêtrière Hospital, Infectious Diseases Department, AP-HP, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Caby
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France.|Virology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
authors.forename: A-G
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Costagliola
authors.affiliation: UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France.|UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France.|Pitié-Salpêtrière Hospital, Infectious Diseases Department, AP-HP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015415:Biomarkers / Q000097:blood*; D054357:Chemokine CXCL10 / Q000097:blood; D054370:Chemokine CXCL9 / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors
keywords: HIV; age; biomarkers; combination antiretroviral therapy; immune activation; inflammation