Human immunodeficiency virus persistence and T-cell activation in blood, rectal, and lymph node tissue in human immunodeficiency virus-infected individuals receiving suppressive antiretroviral therapy

Gabriela Khoury, Rémi Fromentin, Ajantha Solomon, Wendy Hartogensis, Marisela Killian, Rebecca Hoh, Ma Somsouk, Peter W. Hunt, Valerie Girling, Elizabeth J Sinclair, Peter Bacchetti, Jenny L. Anderson, Frederick M. Hecht, Steven G. Deeks, Paul U. Cameron, Nicolas Chomont, Sharon R. Lewin

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30 Citations (Scopus)

Abstract

Background. Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence. Methods. Using flow cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48), lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated unspliced HIV RNA were quantified. Results. CD4+ T cells from rectal tissue had a higher frequency of integrated HIV DNA compared with blood (4.26 fold-change in DNA; 95% confidence interval [CI] = 2.61-7.00; P <.001) and LN (2.32 fold-change in DNA; 95% CI = 1.22-4.41; P =.01). In rectal tissue, there were positive associations between integrated HIV DNA with PD-1+ CD4+ T-cells (1.44 fold-change in integrated HIV DNA per 10-unit increase in PD-1+ CD4+ T cells; 95% CI = 1.01-2.05; P =.045) and CD38+HLA-DR+ CD8+ T cells (1.40 foldchange in integrated HIV DNA per 1-unit increase in CD38+HLA-DR+ CD8+ T cells; 95% CI = 1.05-1.86; P =.02). Both associations were independent of current and nadir CD4+ T-cell counts. Conclusions. During ART, rectal tissue is an important reservoir for HIV persistence with a high frequency of activated CD4+ and CD8+ T cells. PD-1 may represent a marker of HIV persistence in rectal tissue.

Original languageEnglish
Pages (from-to)911-919
Number of pages9
JournalJournal of Infectious Diseases
Volume215
Issue number6
DOIs
Publication statusPublished - 15 Mar 2017

Keywords

  • Antiretroviral therapy
  • HIV
  • HIV persistence
  • Lymph node
  • PD-1
  • Rectum
  • Reservoir
  • T-cell activation

Cite this

Khoury, G., Fromentin, R., Solomon, A., Hartogensis, W., Killian, M., Hoh, R., Somsouk, M., Hunt, P. W., Girling, V., Sinclair, E. J., Bacchetti, P., Anderson, J. L., Hecht, F. M., Deeks, S. G., Cameron, P. U., Chomont, N., & Lewin, S. R. (2017). Human immunodeficiency virus persistence and T-cell activation in blood, rectal, and lymph node tissue in human immunodeficiency virus-infected individuals receiving suppressive antiretroviral therapy. Journal of Infectious Diseases, 215(6), 911-919. https://doi.org/10.1093/infdis/jix039