AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Miller, V.
Right arrow Articles by Staszewski, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miller, V.
Right arrow Articles by Staszewski, S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 1998, p. 3123-3129, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Patterns of Resistance and Cross-Resistance to Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors in Patients Treated with the Nonnucleoside Reverse Transcriptase Inhibitor Loviride

Veronica Miller,1,* Marie-Pierre de Béthune,2 Astrid Kober,1 Martin Stürmer,1 Kurt Hertogs,3 Rudi Pauwels,3 Paul Stoffels,4,dagger and Schlomo Staszewski1

Zentrum der Inneren Medizin, J. W. Goethe Universität, Frankfurt, Germany,1 and TIBOTEC, Institute for Antiviral Research,2 and VIRCO, Central Virological Laboratory,3 B-2800 Mechelen, and Janssen Research Foundation, B-2340 Beerse,4 Belgium

Received 26 May 1998/Returned for modification 29 August 1998/Accepted 22 September 1998

Human immunodeficiency virus type 1 (HIV-1) strains resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) may easily be selected for in vitro and in vivo under a suboptimal therapy regimen. Although cross-resistance is extensive within this class of compounds, newer NNRTIs were reported to retain activity against laboratory strains containing defined resistance-associated mutations. We have characterized HIV-1 resistance to loviride and the extent of cross-resistance to nevirapine, delavirdine, efavirenz, HBY-097, and tivirapine in a set of 24 clinical samples from patients treated with long-term loviride monotherapy by using a recombinant virus assay. Genotypic changes associated with resistance were analyzed by population sequencing. Overall, phenotypic resistance to loviride ranged from 0.04 to 3.47 log10-fold. Resistance was observed in samples from patients who had discontinued loviride for up to 27 months. Cross-resistance to the other compounds was extensive; however, fold resistance to efavirenz was significantly lower than fold resistance to nevirapine. No genotypic changes were detected in three samples; these were sensitive to all of the NNRTIs tested. The most common genotypic change was the K103N substitution. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTI.

* Corresponding author. Mailing address: Klinikum der J. W. Goethe Universität, Zentrum der Inneren Medizin, Infektionsambulanz, Haus 68, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Phone: (49) 69-6301-7680. Fax: (49) 69-6301-5712. E-mail: miller{at}em.uni-frankfurt.de.

dagger Present address: VIRCO, Central Virological Laboratory, B-2800 Mechelen, Belgium.

Antimicrobial Agents and Chemotherapy, December 1998, p. 3123-3129, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 1998 by the American Society for Microbiology. All rights reserved.