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. (7th February 2017)

• Record Type: Journal Article
• Authors: Khoury, Gabriela; Fromentin, Rémi; Solomon, Ajantha; Hartogensis, Wendy; Killian, Marisela; Hoh, Rebecca; Somsouk, Ma; Hunt, Peter W.; Girling, Valerie; Sinclair, Elizabeth; Bacchetti, Peter; Anderson, Jenny L.; Hecht, Frederick M.; Deeks, Steven G.; Cameron, Paul U.; Chomont, Nicolas; Lewin, Sharon R.
• Is Part Of: Journal of infectious diseases. Volume 215:Number 6(2017:Mar. 15)
• Page Start: 911
• Page End: 919
• Publication Date: 2017-02-07
• Subjects: HIV -- HIV persistence -- Antiretroviral therapy -- T-cell activation -- lymph node -- rectum -- reservoir -- PD-1.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix039
• Languages: English
• ISSNs: 0022-1899

Abstract

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 fold-change 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.