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Antimicrobial Agents and Chemotherapy, August 2001, p. 2276-2279, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2276-2279.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Variants Other than Aspartic Acid at Codon 69 of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Gene Affect Susceptibility to Nucleoside Analogs

Mark A. Winters* and Thomas C. Merigan

Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California

Received 5 January 2001/Returned for modification 27 March 2001/Accepted 18 May 2001

The T69D mutation in the human immunodeficiency virus type 1 reverse transcriptase (RT) gene has been associated with reduced susceptibility to dideoxycytosine (ddC); however, several other mutations at codon 69 have been observed in antiretroviral drug-treated patients. The Stanford HIV RT and Protease Sequence Database was interrogated and showed that 23% of patients treated with nucleoside RT inhibitors (NRTI) had mutations at codon 69. These variants included T69N, -S, -A, -G, -E, -I, and -K mutations that were present in patients treated with NRTI but not in drug-naive patients. Treatment history information showed that a substantial percentage of these codon 69 changes occurred in patients administered non-ddC-containing regimens. Different and specific patterns of other RT gene mutations were associated with the various codon 69 mutations. Drug susceptibility assays showed that viral constructs containing codon 69 variants could have reduced susceptibility to ddC and other RT inhibitors. These results suggest that the T69D mutation is not the only codon 69 variant associated with drug resistance and that ddC is not the only drug affected.

* Corresponding author. Mailing address: Stanford Medical Center, Room S146, 300 Pasteur Dr., Stanford, CA 94305. Phone: (650) 723-5715. Fax: (650) 725-2395. E-mail: mark.winters{at}stanford.edu.

Antimicrobial Agents and Chemotherapy, August 2001, p. 2276-2279, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2276-2279.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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