title: Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.
abstract: BACKGROUND
  It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs).
  
  
  METHODS
  In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control.
  
  
  RESULTS
  Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups.
  
  
  CONCLUSIONS
  Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens.
  
  
  BACKGROUND
  NCT00811954 and NCT00851799.
authors.affiliation: David Geffen School of Medicine at the University of California, Los Angeles.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Thuy Tien T
authors.initials: TT
authors.lastname: Tran
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Carlee
authors.initials: C
authors.lastname: Moser
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.affiliation: Keck School of Medicine at the University of Southern California, Los Angeles.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dube
authors.affiliation: Northwestern University, Evanston, Illinois.
authors.forename: Robert
authors.initials: R
authors.lastname: Murphy
authors.affiliation: David Geffen School of Medicine at the University of California, Los Angeles.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.affiliation: David Geffen School of Medicine at the University of California, Los Angeles.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, Ohio University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000069454:Darunavir / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D000069454:Darunavir
keywords: human immunodeficiency virus; immune activation; inflammation; integrase inhibitors; protease inhibitors