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

Authors

• Jacob D. Estes, Frederick National Laboratory
• Cavan Reilly, University of Minnesota
• Charles M. Trubey, Frederick National Laboratory
• Courtney V. Fletcher, University of Nebraska Medical CenterFollow
• Theodore J. Cory, University of Nebraska Medical Center
• Michael Piatak Jr., Frederick National Laboratory
• Samuel Russ, University of Minnesota
• Jodi Anderson, University of Minnesota
• Thomas G. Reimann, University of Minnesota
• Robert Star, National Institutes of Health
• Anthony Smith, University of MinnesotaFollow
• Russell P. Tracy, University of Vermont
• Anna Berglund, University of Minnesota
• Thomas Schmidt, University of Minnesota
• Vicky Coalter, Frederick National Laboratory
• Elena Chertova, Frederick National Laboratory
• Jeremy Smedley, Frederick National Laboratory
• Ashley T. Haase, University of MinnesotaFollow
• Jeffrey D. Lifson, Frederick National Laboratory
• Timothy W. Schacker, University of MinnesotaFollow

Date of this Version

2014

Citation

The Journal of Infectious Diseases^®; DOI: 10.1093/infdis/jiu519

Comments

U.S. Government Work

Abstract

Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have 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.