Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4R T cells in HIV-infected individuals on antiretroviral therapy

Gabriela Khoury, Jenny L. Anderson, Rémi Fromentin, Wendy Hartogenesis, Miranda Z. Smith, Peter Bacchetti, Frederick M. Hecht, Nicolas Chomont, Paul U. Cameron, Steven G. Deeks, Sharon R. Lewin

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40 Citations (Scopus)

Abstract

Background: 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. Objective: To determine if CKR identify CD4+ T cells enriched for HIV in HIV-infected individuals receiving suppressive antiretroviral therapy (ART). Design: 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. Methods: 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. Results: 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. Conclusion: CXCR3 and CCR6 coexpression defines a subset of CD4+ T cells that are preferentially enriched for HIV DNA in HIV-infected individuals on ART.

Original languageEnglish
Pages (from-to)1511-1520
Number of pages10
JournalAIDS
Volume30
Issue number10
DOIs
Publication statusPublished - 19 Jun 2016

Keywords

  • CCR5
  • CCR6
  • chemokine receptors
  • chemokines
  • CXCR3
  • HIV latency
  • HIV reservoir

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