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Journal of Virology, July 1999, p. 6197-6202, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification of Biased Amino Acid Substitution Patterns in Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Protease Inhibitors

Robert W. Shafer,1,* Phillip Hsu,2 Amy K. Patick,3 Charles Craig,4 and Volker Brendel5

Division of Infectious Diseases, Stanford University Medical Center,1 and Stanford University,2 Stanford, California 94305; Agouron Pharmaceuticals, Inc., San Diego, California 921213; Department of Zoology and Genetics, Iowa State University, Ames, Iowa 50011-32605; and Roche Discovery Welwyn, Welwyn Garden City, Hertsfordshire, United Kingdom4

Received 21 July 1998/Accepted 26 March 1999

Human immunodeficiency virus type 1 (HIV-1) amino acid substitutions observed during antiretroviral drug therapy may be caused by drug selection, non-drug-related evolution, or sampling error introduced by the sequencing process. We analyzed HIV-1 sequences from 371 untreated patients and from 178 patients receiving a single protease inhibitor. Amino acid substitution patterns during treatment were compared with inferred substitution patterns arising evolutionarily without treatment. Our results suggest that most treatment-associated amino acid substitutions are caused by selective drug pressure, including substitutions not previously associated with drug resistance.

* Corresponding author. Mailing address: Division of Infectious Diseases, S-156, Stanford University Medical Center, Room S156, 300 Pasteur Dr., Stanford, CA 94305-5107. Phone: (650) 725-2946. Fax: (650) 725-2395. E-mail: rshafer{at}cmgm.stanford.edu.

Journal of Virology, July 1999, p. 6197-6202, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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