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 Servais, J.
Right arrow Articles by Schmit, J.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Servais, J.
Right arrow Articles by Schmit, J.-C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2001, p. 893-900, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.893-900.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Variant Human Immunodeficiency Virus Type 1 Proteases and Response to Combination Therapy Including a Protease Inhibitor

Jean Servais,1,* Christine Lambert,1 Elodie Fontaine,1 Jean-Marc Plesséria,1 Isabelle Robert,1 Vic Arendt,1,2 Thérèse Staub,1,2 François Schneider,1,3 Robert Hemmer,1,2 Guy Burtonboy,4 and Jean-Claude Schmit1,2

Laboratoire de Rétrovirologie, Centre de Recherche Public-Santé,1 Service National des Maladies Infectieuses, Centre Hospitalier de Luxembourg,2 and Laboratoire National de Santé,3 Luxembourg, Luxembourg, and Université Catholique de Louvain, Unité de Virologie Médicale, Brussels, Belgium4

Received 24 March 2000/Returned for modification 22 June 2000/Accepted 19 December 2000

The objective of this observational study was to assess the genetic variability in the human immunodeficiency virus (HIV) protease gene from HIV type 1 (HIV-1)-positive (clade B), protease inhibitor-naïve patients and to evaluate its association with the subsequent effectiveness of a protease inhibitor-containing triple-drug regimen. The protease gene was sequenced from plasma-derived virus from 116 protease inhibitor-naïve patients. The virological response to a triple-drug regimen containing indinavir, ritonavir, or saquinavir was evaluated every 3 months for as long as 2 years (n = 40). A total of 36 different amino acid substitutions compared to the reference sequence (HIV-1 HXB2) were detected. No substitutions at the active site similar to the primary resistance mutations were found. The most frequent substitutions (prevalence, >10%) at baseline were located at codons 15, 13, 12, 62, 36, 64, 41, 35, 3, 93, 77, 63, and 37 (in ascending order of frequency). The mean number of polymorphisms was 4.2. A relatively poorer response to therapy was associated with a high number of baseline polymorphisms and, to a lesser extent, with the presence of I93L at baseline in comparison with the wild-type virus. A71V/T was slightly associated with a poorer response to first-line ritonavir-based therapy. In summary, within clade B viruses, protease gene natural polymorphisms are common. There is evidence suggesting that treatment response is associated with this genetic background, but most of the specific contributors could not be firmly identified. I93L, occurring in about 30% of untreated patients, may play a role, as A71V/T possibly does in ritonavir-treated patients.

* Corresponding author. Mailing address: Laboratoire de Rétrovirologie, CRP-Santé, 4 rue E. Barblé, L-1200 Luxembourg, Luxembourg. Phone: 352-44116105. Fax: 352-44116113. E-mail: servais.j{at}retrovirology.lu.

Antimicrobial Agents and Chemotherapy, March 2001, p. 893-900, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.893-900.2001
Copyright © 2001, 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 © 2001 by the American Society for Microbiology. All rights reserved.