Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy

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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.

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