Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy.

Jacob D Estes, Cavan Reilly, Charles M Trubey, Courtney V Fletcher, Theodore J Cory, Michael Piatak, Samuel Russ, Jodi Anderson, Thomas G Reimann, Robert Star, Anthony Smith, Russell P Tracy, Anna Berglund, Thomas Schmidt, Vicky Coalter, Elena Chertova, Jeremy Smedley, Ashley T Haase, Jeffrey D Lifson, Timothy W Schacker

Index: J. Infect. Dis. 211(5) , 744-54, (2015)

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Abstract

Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4(+) T cells/µL, and CD4(+) T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4(+) T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4(+) T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4(+) T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.