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Journal of Virology, May 2004, p. 5324-5337, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5324-5337.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CD8+-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment

Koen K. A. Van Rompay,1* Raman P. Singh,1 Bapi Pahar,1 Donald L. Sodora,2 Casey Wingfield,3 Jonathan R. Lawson,1 Marta L. Marthas,1 and Norbert Bischofberger4

California National Primate Research Center, University of California, Davis,1 Bayer Diagnostics Reference Testing Lab, Bayer Diagnostics, Berkeley,3 Gilead Sciences, Foster City, California,4 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas2

Received 1 October 2003/ Accepted 6 January 2004

The ability of tenofovir to suppress viremia in simian immunodeficiency virus (SIV)-infected macaques for years despite the presence of virulent viral mutants with reduced in vitro susceptibility is unprecedented in this animal model. In vivo cell depletion experiments demonstrate that tenofovir's ability to suppress viremia during acute and chronic infection is significantly dependent on the presence of CD8+ lymphocytes. Continuous tenofovir treatment was required to maintain low viremia. Although it is unclear whether this immune-mediated suppression of viremia is linked to tenofovir's direct antiviral efficacy or is due to independent immunomodulatory effects, these studies prove the concept that antiviral immune responses can play a crucial role in suppressing viremia during anti-human immunodeficiency virus drug therapy.

* Corresponding author. Mailing address: California National Primate Research Center, University of California, Davis, CA 95616. Phone: (530) 752-5281. Fax: (530) 754-4411. E-mail: kkvanrompay{at}ucdavis.edu.

Journal of Virology, May 2004, p. 5324-5337, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5324-5337.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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Copyright © 2004 by the American Society for Microbiology. All rights reserved.