title: Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy.
abstract: HIV latent infection can be established in vitro by treating resting CD4 T cells with chemokines that bind to chemokine receptors (CKR), CCR7, CXCR3, and CCR6, highly expressed on T cells.
  
  
  
  To determine if CKR identify CD4 T cells enriched for HIV in HIV-infected individuals receiving suppressive antiretroviral therapy (ART).
  
  
  
  A cross-sectional study of CKR expression and HIV persistence in blood from HIV-infected individuals on suppressive ART for more than 3 years (n = 48). A subset of 20 individuals underwent leukapheresis and sorting of specific CD4 T-cell subsets.
  
  
  
  We used flow cytometry to quantify CCR5, CCR6, CXCR3, and CXCR5 expression on CD4 T cells. HIV persistence was quantified using real-time Polymerase Chain Reaction to detect total, integrated HIV DNA, 2-long terminal repeat circles and cell-associated unspliced (CA-US) HIV RNA in total CD4 T cells from blood or sorted T-cell subsets. Associations between CKR and HIV persistence in CD4 T cells in blood were determined using regression models and adjusted for current and nadir CD4 T-cell counts.
  
  
  
  The frequency of cells harbouring integrated HIV DNA was inversely associated with current CD4 T-cell count and positively associated with CCR5+ CD4 T cells, CXCR3+CCR6+ and CXCR3+CCR6- expression on total memory CD4 T cells (P < 0.001, 0.048, 0.015, and 0.016, respectively). CXCR3+CCR6+ CM CD4 T cells contained the highest amount of integrated HIV DNA and lowest ratio of CA-US HIV RNA to DNA compared to all T-cell subsets examined.
  
  
  
  CXCR3 and CCR6 coexpression defines a subset of CD4 T cells that are preferentially enriched for HIV DNA in HIV-infected individuals on ART.
authors.affiliation: aThe Peter Doherty Institute for Infection and Immunity, University of MelbournebDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, AustraliacDepartment of Microbiology, Infectiology and Immunology, Université de Montréal, Faculty of Medicine, and Centre de Recherche du CHUM, Montréal, Quebec, CanadadDepartment of MedicineeDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Khoury
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Rémi
authors.initials: R
authors.lastname: Fromentin
authors.forename: Wendy
authors.initials: W
authors.lastname: Hartogenesis
authors.forename: Miranda Z
authors.initials: MZ
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000032:analysis*; D054367:Receptors, CXCR3 / Q000032:analysis*; D000072230:Sustained Virologic Response; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000821:virology; D017735:Virus Latency
chemical_list: D044966:Anti-Retroviral Agents; C106311:CCR6 protein, human; C515187:CXCR3 protein, human; D004279:DNA, Viral; D054399:Receptors, CCR6; D054367:Receptors, CXCR3