Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques

Maria Pino, Amélie Pagliuzza, M. Betina Pampena, Claire Deleage, Elise G. Viox, Kevin Nguyen, Inbo Shim, Adam Zhang, Justin L. Harper, Sadia Samer, Colin T. King, Barbara Cervasi, Kiran P. Gill, Stephanie Ehnert, Sherrie M. Jean, Michael L. Freeman, Jeffrey D. Lifson, Deanna Kulpa, Michael R. Betts, Nicolas Chomont, Michael M. Lederman and Mirko Paiardini ()
Additional contact information
Maria Pino: Emory University
Amélie Pagliuzza: Université de Montréal
M. Betina Pampena: University of Pennsylvania
Claire Deleage: Leidos Biomedical Research, Inc.
Elise G. Viox: Emory University
Kevin Nguyen: Emory University
Inbo Shim: Emory University
Adam Zhang: Emory University
Justin L. Harper: Emory University
Sadia Samer: Emory University
Colin T. King: Emory University
Barbara Cervasi: Emory University
Kiran P. Gill: Emory University
Stephanie Ehnert: Emory University
Sherrie M. Jean: Emory University
Michael L. Freeman: Case Western Reserve University/University Hospitals Cleveland Medical Center
Jeffrey D. Lifson: Leidos Biomedical Research, Inc.
Deanna Kulpa: Emory University
Michael R. Betts: University of Pennsylvania
Nicolas Chomont: Université de Montréal
Michael M. Lederman: Case Western Reserve University/University Hospitals Cleveland Medical Center
Mirko Paiardini: Emory University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Antiretroviral therapy (ART) is not curative due to the persistence of a reservoir of HIV-infected cells, particularly in tissues such as lymph nodes, with the potential to cause viral rebound after treatment cessation. In this study, fingolimod (FTY720), a lysophospholipid sphingosine-1-phosphate receptor modulator is administered to SIV-infected rhesus macaques at initiation of ART to block the egress from lymphoid tissues of natural killer and T-cells, thereby promoting proximity between cytolytic cells and infected CD4+ T-cells. When compared with the ART-only controls, FTY720 treatment during the initial weeks of ART induces a profound lymphopenia and increases frequencies of CD8+ T-cells expressing perforin in lymph nodes, but not their killing capacity; FTY720 also increases frequencies of cytolytic NK cells in lymph nodes. This increase of cytolytic cells, however, does not limit measures of viral persistence during ART, including intact proviral genomes. After ART interruption, a subset of animals that initially receives FTY720 displays a modest delay in viral rebound, with reduced plasma viremia and frequencies of infected T follicular helper cells. Further research is needed to optimize the potential utility of FTY720 when coupled with strategies that boost the antiviral function of T-cells in lymphoid tissues.

Date: 2022
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DOI: 10.1038/s41467-022-32698-y

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