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Antimicrobial Agents and Chemotherapy, March 2000, p. 783-786, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antiviral Activity of 2'-Deoxy-3'-Oxa-4'-Thiocytidine (BCH-10652) against Lamivudine-Resistant Human Immunodeficiency Virus Type 1 in SCID-hu Thy/Liv Mice

Cheryl A. Stoddart,1,* Mary E. Moreno,1 Valerie D. Linquist-Stepps,1 Christopher Bare,1 Mark R. Bogan,1 Alberto Gobbi,1,dagger Robert W. Buckheit Jr.,2 Jean Bedard,3 Robert F. Rando,3 and Joseph M. McCune1,4

Antiviral Drug Research Division, Gladstone Institute of Virology and Immunology,1 and Departments of Medicine and Microbiology and Immunology,4 University of California, San Francisco, California; Southern Research Institute, Frederick, Maryland 21701-4756,2 and Department of Virology, BioChem Pharma Inc., Laval, Quebec, Canada H7V 4A73

Received 21 July 1999/Returned for modification 22 October 1999/Accepted 29 November 1999

Oral administration of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652), a nucleoside analog structurally similar to lamivudine (3TC), caused dose-dependent inhibition of viral replication in SCID-hu Thy/Liv mice infected with human immunodeficiency virus type 1 NL4-3 and with an NL4-3 clone containing the M184V mutation in reverse transcriptase that confers resistance to 3TC. These experiments demonstrate the utility of this mouse model for evaluating drug resistance and for performing direct comparisons between antiviral compounds in vivo.

* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94141-9100. Phone: (415) 695-3813. Fax: (415) 826-8449. E-mail: cstoddart{at}gladstone.ucsf.edu.

dagger Present address: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.

Antimicrobial Agents and Chemotherapy, March 2000, p. 783-786, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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