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Antimicrobial Agents and Chemotherapy, July 2003, p. 2376-2379, Vol. 47, No. 7
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.7.2376-2379.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
The M184V Substitution in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Delays the Development of Resistance to Amprenavir and Efavirenz in Subtype B and C Clinical Isolates
Karidia Diallo,1,2 Bluma Brenner,1 Maureen Oliveira,1 Daniela Moisi,1 Mervi Detorio,1 Matthias Götte,1,2,3 and Mark A. Wainberg1,2,3*
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital,1
Department of Microbiology and Immunology,2
Department of Experimental Medicine, McGill University, Montreal, H3T 1E2 Quebec, Canada3
Received 14 October 2002/
Returned for modification 23 December 2002/
Accepted 9 April 2003
The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), encoding high-level resistance to lamivudine (3TC), results in decreased HIV-1 replicative capacity, diminished RT processivity, and increased RT fidelity in biochemical assays. We assessed the effect of M184V on the development of resistance to the nonnucleoside RT inhibitors efavirenz (EFV) and nevirapine, and to the protease inhibitor amprenavir (APV) in tissue culture. Genotypic analysis revealed differences in EFV resistance-conferring mutations in subtype B (K103N) versus subtype C (V106 M), and the appearance of both was significantly delayed in the M184V-containing variants compared with the wild type (WT). Similarly, there was a marked delay in the emergence of mutations associated with APV resistance (I54 M/L/V) in subtype B viruses harboring M184V compared with paired WT viral isolates.
* Corresponding author. Mailing address: McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, 3755 Cote Ste-Catherine Rd., Montréal, Québec, Canada, H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7537. E-mail: mark.wainberg{at}mcgill.ca.
Dedicated to the memory of James-Paul Marois.
Antimicrobial Agents and Chemotherapy, July 2003, p. 2376-2379, Vol. 47, No. 7
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.7.2376-2379.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.