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Journal of Virology, April 1999, p. 2947-2955, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Early Short-Term 9-[2-(R)-(Phosphonomethoxy)Propyl]Adenine Treatment Favorably Alters the Subsequent Disease Course in Simian Immunodeficiency Virus-Infected Newborn Rhesus Macaques

Koen K. A. van Rompay,1 Peter J. Dailey,2 Ross P. Tarara,1 Don R. Canfield,1 Nancy L. Aguirre,1 Julie M. Cherrington,3 Patrick D. Lamy,3 Norbert Bischofberger,3 Niels C. Pedersen,4 and Marta L. Marthas1,*

California Regional Primate Research Center1 and Department of Veterinary Medicine and Epidemiology,4 University of California, Davis, California 95616; Chiron Diagnostics, Emeryville, California 946082; and Gilead Sciences, Foster City, California 944043

Received 16 October 1998/Accepted 6 January 1999

Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful animal model of human pediatric AIDS to study disease pathogenesis and to develop intervention strategies aimed at delaying disease. In the present study, we demonstrate that very early events of infection greatly determine the ultimate disease course, as short-term antiviral drug administration during the initial viremia stage significantly delayed the onset of AIDS. Fourteen newborn macaques were inoculated orally with uncloned, highly virulent SIVmac251. The four untreated control animals showed persistently high virus levels and poor antiviral immune responses; they developed fatal immunodeficiency within 15 weeks. In contrast, SIV-infected newborn macaques which were started on 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) treatment at 5 days of age and continued for either 14 or 60 days showed reduced virus levels and enhanced antiviral immune responses. This short-term PMPA treatment did not induce detectable emergence of SIV mutants with reduced in vitro susceptibility to PMPA. Although viremia increased in most animals after PMPA treatment was withdrawn, all animals remained disease-free for at least 6 months. Our data suggest that short-term treatment with a potent antiviral drug regimen during the initial viremia will significantly prolong AIDS-free survival for HIV-infected infants and adults.

* Corresponding author. Mailing address: California Regional Primate Research Center, University of California, Davis, County Rd. 98 and Hutchison, Davis, CA 95616. Phone: (530) 752-0447. Fax: (530) 752-2880. E-mail: mlmarthas{at}ucdavis.edu.

Journal of Virology, April 1999, p. 2947-2955, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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