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HIV DNA reservoir and elevated PD‐1 expression of CD4 T‐cell subsets particularly persist in the terminal ileum of HIV‐positive patients despite cART

Abstract : Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed-death-1 (PD-1) has been linked to the HIV reservoir and T-cell immune dysfunction. We thus evaluated PD-1 expression and cell-associated HIV DNA in memory CD4 T-cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV-positive patients to identify associations between PD-1 and HIV reservoir in other sites. Methods Using mononuclear cells from PB, TI and RE of untreated HIV-positive (N = 6), treated (n = 18) HIV-positive and uninfected individuals (n = 16), we identified and sorted distinct memory CD4 T-cell subsets by flow cytometry, quantified their cell-associated HIV DNA using quantitative PCR and assessed PD-1 expression levels using geometric mean fluorescence intensity. Combined HIV-1 RNA in situ hybridization and immunohistochemistry was performed on ileal biopsy sections. Results Combined antiretroviral therapy (cART)-treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD-1 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment-naïve patients HIV DNA levels in memory CD4 T-cell subsets were high in PB and TI. Conclusion Elevated PD-1 expression on memory CD4 T-cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T-cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03244353
Contributor : Marie-Christine Vougny <>
Submitted on : Tuesday, June 1, 2021 - 10:57:24 AM
Last modification on : Thursday, June 10, 2021 - 3:23:15 PM

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C Horn, M Augustin, Ms Ercanoglu, E Heger, E Knops, et al.. HIV DNA reservoir and elevated PD‐1 expression of CD4 T‐cell subsets particularly persist in the terminal ileum of HIV‐positive patients despite cART. HIV Medicine, Wiley, 2021, 22 (5), pp.397-408. ⟨10.1111/hiv.13031⟩. ⟨pasteur-03244353⟩

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