title: Differential Reduction in Monocyte Activation and Vascular Inflammation With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among HIV-Infected Individuals.
abstract: BACKGROUND
  Little is known about how different antiretrovirals effect inflammation and monocyte activation in human immunodeficiency virus (HIV) infection.
  
  
  METHODS
  We examined plasma specimens obtained during a randomized, double-blinded trial in antiretroviral therapy (ART)-naive HIV-infected adults which compared the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) with that of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). From a random sample achieving an HIV type 1 RNA load of <50 copies/mL by week 48, changes over 24 and 48 weeks in levels of biomarkers of monocyte activation (soluble CD14 [sCD14] and soluble CD163 [sCD163]), systemic inflammation (soluble tumor necrosis factor α receptor I [sTNF-RI], interleukin 6 [IL-6], and high-sensitivity C-reactive protein [hsCRP]), and vascular inflammation (lipoprotein-associated phospholipase A2 [Lp-PLA2]) were compared. Multivariable linear regression was used.
  
  
  RESULTS
  A total of 200 participants were included. Significant differences favoring EVG/c/FTC/TDF were noted for changes in sCD14, hsCRP, and Lp-PLA2 levels. Factors independently associated with a larger decrease in the sCD14 level included random assignment to receive EVG/c/FTC/TDF, higher baseline sCD14 level, and larger decreases in hsCRP and sCD163 levels; factors associated with a larger Lp-PLA2 decrease included higher baseline Lp-PLA2 and IL-6 levels, smaller increases in total cholesterol and triglycerides levels, a larger decrease in the sCD14 level, and a smaller decrease in the sCD163 level.
  
  
  CONCLUSIONS
  EVG/c/FTC/TDF led to greater decreases in sCD14, hsCRP, and Lp-PLA2 levels, compared with EFV/FTC/TDF. Randomization group independently predicted the change in sCD14 level, and changes in monocyte activation independently predicted the change in Lp-PLA2 level. There appears to be a more favorable effect of the integrase inhibitor EVG over efavirenz on immune activation, which may affect vascular inflammation.
authors.affiliation: Case Western Reserve University School of Medicine MetroHealth Medical Center.
authors.forename: Corrilynn O
authors.initials: CO
authors.lastname: Hileman
authors.affiliation: University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Bruce
authors.initials: B
authors.lastname: Kinley
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Valeska
authors.initials: V
authors.lastname: Scharen-Guivel
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Kathy
authors.initials: K
authors.lastname: Melbourne
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Javier
authors.initials: J
authors.lastname: Szwarcberg
authors.affiliation: Case Western Reserve University School of Medicine.
authors.forename: Janet
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Case Western Reserve University School of Medicine University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Case Western Reserve University School of Medicine University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Mccomsey
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000276:immunology*; D000328:Adult; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*
chemical_list: D019428:HIV Integrase Inhibitors; D018950:Lipopolysaccharide Receptors; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
keywords: HIV infection; antiretroviral-naive; monocyte activation; systemic inflammation; vascular inflammation