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Antimicrobial Agents and Chemotherapy, November 1998, p. 3038-3043, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Coresistance to Zidovudine and Foscarnet Is Associated with Multiple Mutations in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Gilda Tachedjian,1,dagger Martyn French,2 and John Mills1,*

National Centre in HIV Virology Research, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria 3078,1 and Department of Clinical Immunology, Royal Perth Hospital, Western Australia 6000,2 Australia

Received 7 April 1998/Returned for modification 29 June 1998/Accepted 29 August 1998

Human immunodeficiency virus type 1 (HIV-1) isolates obtained from a patient with AIDS were assessed for coresistance to foscarnet and zidovudine. An HIV-1 strain (AP20) coresistant to foscarnet and zidovudine was isolated after 20 months of continuous combination therapy. The reverse transcriptase (RT) gene of AP20 had 41 substitutions which were different from the HXB2-D sequence and 9 that were different from the sequence of its foscarnet-sensitive, zidovudine-resistant progenitor virus (AP6). Six of these mutations were nonpolymorphic (T39A, V108I, K166R, K219R, K223Q, and L228R). Both strains had the conventional mutations mediating zidovudine resistance. In vivo selection may result in HIV-1 strains that are coresistant to foscarnet and zidovudine, but coresistance appears to require a complex evolutionary path and multiple RT mutations.

* Corresponding author. Mailing address: National Centre in HIV Virology Research, Macfarlane Burnet Centre for Medical Research, P.O. Box 254, Fairfield, Victoria, Australia 3078. Phone: (61) 3 9282 2123. Fax: (61) 3 9282 2126. E-mail: mills{at}burnet.edu.au.

dagger Present address: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032.

Antimicrobial Agents and Chemotherapy, November 1998, p. 3038-3043, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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