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Journal of Clinical Microbiology, March 2001, p. 1124-1129, Vol. 39, No. 3
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.3.1124-1129.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Evolution of the Human Immunodeficiency Virus Type 1 Gag-Protease Region and Maintenance of Reverse Transcriptase Resistance following Prolonged Drug Exposure

Simona La Seta Catamancio, Maria Pia De Pasquale, Paola Citterio, Semir Kurtagic, Massimo Galli, and Stefano Rusconi^*

Istituto di Malattie Infettive e Tropicali, Università di Milano, Ospedale Luigi Sacco, Milan, Italy

Received 21 April 2000/Returned for modification 24 August 2000/Accepted 15 December 2000

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions.

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^* Corresponding author. Mailing address: Istituto di Malattie Infettive e Tropicali, Università di Milano, Ospedale Luigi Sacco, via GB Grassi 74, 20157 Milan, Italy. Phone: 011.39.02.39043350. Fax: 011.39.02.3560805. E-mail: rusconi{at}mailserver.unimi.it.

This report is dedicated to the memory of Alessandro Caporali.

Present address: Infectious Disease Unit, Massachusetts General Hospital-East, Charlestown, MA 02129.

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Journal of Clinical Microbiology, March 2001, p. 1124-1129, Vol. 39, No. 3
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.3.1124-1129.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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