Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy. (19th June 2016)

• Record Type: Journal Article
• Authors: Khoury, Gabriela; Anderson, Jenny L.; Fromentin, Rémi; Hartogenesis, Wendy; Smith, Miranda Z.; Bacchetti, Peter; Hecht, Frederick M.; Chomont, Nicolas; Cameron, Paul U.; Deeks, Steven G.; Lewin, Sharon R.
• Is Part Of: AIDS. Volume 30:Number 10(2016)
• Publication Date: 2016-06-19
• Subjects: CCR5 -- CCR6 -- chemokine receptors -- chemokines -- CXCR3 -- HIV latency -- HIV reservoir; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001029
• Languages: English
• ISSNs: 0269-9370

Abstract

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. Abstract : Supplemental Digital Content is available in the text