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

نویسندگان

  • 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
چکیده

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.

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Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4<sup>+</sup> T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

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عنوان ژورنال:
  • The Journal of infectious diseases

دوره 211 5  شماره 

صفحات  -

تاریخ انتشار 2015