title: Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals.
abstract: BACKGROUND
  HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies.
  
  
  METHODS
  Longitudinal plasma samples (0-48 weeks) from the IntegRal (n = 67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts<350 cells/µl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis.
  
  
  RESULTS
  At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P = 0.040).
  
  
  CONCLUSIONS
  The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; VA San Diego Healthcare System and Departments of Pathology and Medicine, University of California San Diego (UCSD), San Diego, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain.
authors.forename: Dan
authors.initials: D
authors.lastname: Ouchi
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marfil
authors.affiliation: "Lluita contra la SIDA" Foundation, University Hospital Germans Trias i Pujol, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Buzón
authors.affiliation: VA San Diego Healthcare System and Departments of Pathology and Medicine, University of California San Diego (UCSD), San Diego, United States of America.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.affiliation: Hematology Department, University Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Orna
authors.affiliation: University of Miami, Miami, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Stevenson
authors.affiliation: Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: "Lluita contra la SIDA" Foundation, University Hospital Germans Trias i Pujol, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain.
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; "Lluita contra la SIDA" Foundation, University Hospital Germans Trias i Pujol, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain.
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D019428:HIV Integrase Inhibitors; D000068898:Raltegravir Potassium