title: Altered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase-Inhibitor-Based Antiretroviral Therapy.
abstract: BACKGROUND
  Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined. Here, we define more completely monocyte phenotype both prior to ART initiation and during 48 weeks of ART.
  
  
  METHODS
  Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment from 29 patients participating in ACTG clinical trial A5248, an open label study of raltegravir/emtricitibine/tenofovir administration. For comparison, cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom had at least two cardiovascular risk factors. Thawed samples were stained for monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40, CD38, CD36, CD13, and CD163 and examined using flow cytometry.
  
  
  RESULTS
  In untreated HIV-1 infection there were perturbations in monocyte subset phenotypes, chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA-DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2 density on inflammatory monocytes (p = 0.045) when compared to the expression and density of these markers in controls' monocytes. We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls. After ART, these perturbations tended to improve, with decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on inflammatory monocytes, and increasing expression and density of CX3CR1 on patrolling monocytes.
  
  
  CONCLUSIONS
  In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating monocyte phenotypes are altered in untreated infection and tend to normalize with ART; the role of these cells in the inflammatory environment of HIV-1 infection warrants further study.
authors.affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Marie R
authors.initials: MR
authors.lastname: McCausland
authors.affiliation: Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Juchnowski
authors.affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America; Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Zidar
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.affiliation: Department of Medicine, Division of Infectious Diseases, John Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Adriana
authors.initials: A
authors.lastname: Andrade
authors.affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
authors.affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active; D000073883:CX3C Chemokine Receptor 1; D002469:Cell Separation; D004338:Drug Combinations; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification*; D000068898:Raltegravir Potassium / Q000627:therapeutic use; D054390:Receptors, CCR2 / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D004338:Drug Combinations; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D019428:HIV Integrase Inhibitors; D006684:HLA-DR Antigens; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D000068898:Raltegravir Potassium