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Antimicrobial Agents and Chemotherapy, March 2006, p. 1092-1095, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.1092-1095.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

In Vitro Development of Resistance to Human Immunodeficiency Virus Protease Inhibitor GW640385

P. J. Yates,1* R. Hazen,2 M. St. Clair,2 L. Boone,2 M. Tisdale,1 and R. C. Elston1

GlaxoSmithKline Inc., Stevenage, United Kingdom,1 GlaxoSmithKline Inc., Research Triangle Park, North Carolina2

Received 11 July 2005/ Returned for modification 9 September 2005/ Accepted 30 December 2005

Development of in vitro resistance to GW640385, a new human immunodeficiency virus type 1 protease inhibitor, was studied. Variants characterized included one with <4-fold resistance and amino acid substitutions Q58E/A71V (protease) and P452K (Gag) and one with >50-fold resistance and amino acid substitutions L10F/G16E/E21K/A28S/M46I/F53L/A71V (protease) and L449F/P453T (Gag). The A28S substitution substantially reduced replication capacity.

* Corresponding author. Mailing address: UK Virology, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom. Phone: 44 1438 763887. Fax: 44 1438 764263. E-mail: pjy29430{at}gsk.com.

Antimicrobial Agents and Chemotherapy, March 2006, p. 1092-1095, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.1092-1095.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hazen, R., Harvey, R., Ferris, R., Craig, C., Yates, P., Griffin, P., Miller, J., Kaldor, I., Ray, J., Samano, V., Furfine, E., Spaltenstein, A., Hale, M., Tung, R., St. Clair, M., Hanlon, M., Boone, L. (2007). In Vitro Antiviral Activity of the Novel, Tyrosyl-Based Human Immunodeficiency Virus (HIV) Type 1 Protease Inhibitor Brecanavir (GW640385) in Combination with Other Antiretrovirals and against a Panel of Protease Inhibitor-Resistant HIV. Antimicrob. Agents Chemother. 51: 3147-3154 [Abstract] [Full Text]  


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