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

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)744-754
Number of pages11
JournalJournal of Infectious Diseases
Volume211
Issue number5
DOIs
StatePublished - 2015

Keywords

  • Fibroblastic reticular cell network
  • Fibrosis
  • HIV
  • Immune reconstitution
  • T-cell depletion

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Estes, J. D., Reilly, C., Trubey, C. M., Fletcher, C. V., Cory, T. J., Piatak, M., Russ, S., Anderson, J., Reimann, T. G., Star, R., Smith, A., Tracy, R. P., Berglund, A., Schmidt, T., Coalter, V., Chertova, E., Smedley, J., Haase, A. T., Lifson, J. D., & Schacker, T. W. (2015). Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy. Journal of Infectious Diseases, 211(5), 744-754. https://doi.org/10.1093/infdis/jiu519