Universität zu Köln

Horn, C., Augustin, M., Ercanoglu, M. S., Heger, E., Knops, E., Bondet, V, Duffy, D., Chon, S-H, Nierhoff, D., Oette, M., Schaefer, H., Vivaldi, C., Held, K., Anderson, J., Geldmacher, C., Suarez, I, Rybniker, J., Klein, F., Faetkenheuer, G., Muller-Trutwin, M. and Lehmann, C. (2021). 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 Med., 22 (5). S. 397 - 409. HOBOKEN: WILEY. ISSN 1468-1293

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Abstract

Objectives 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-naive 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Horn, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Augustin, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ercanoglu, M. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heger, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knops, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bondet, V UNSPECIFIED UNSPECIFIED UNSPECIFIED Duffy, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chon, S-H UNSPECIFIED UNSPECIFIED UNSPECIFIED Nierhoff, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oette, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vivaldi, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Held, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Anderson, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geldmacher, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Suarez, I UNSPECIFIED UNSPECIFIED UNSPECIFIED Rybniker, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Faetkenheuer, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Muller-Trutwin, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-593308
DOI:	10.1111/hiv.13031
Journal or Publication Title:	HIV Med.
Volume:	22
Number:	5
Page Range:	S. 397 - 409
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1468-1293
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INFECTED INDIVIDUALS; IMMUNE ACTIVATION; PERIPHERAL-BLOOD; IN-VIVO; REPLICATION; GUT; TISSUE; EXHAUSTION; DYNAMICS; BURDEN Multiple languages Infectious Diseases Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59330