Document Detail


Stavudine resistance: an update on susceptibility following prolonged therapy.
MedLine Citation:
PMID:  10682125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The current report summarizes the available published and unpublished data from several investigators on resistance in clinical isolates following prolonged stavudine therapy. Results suggest that stavudine resistance is both modest in degree and infrequent in appearance. Phenotypic evaluation of 61 patients on stavudine therapy showed only modest changes in drug sensitivity following up to 29 months of treatment. The post-treatment isolates from 15 patients exhibited an increase in EC50 value > fourfold (level above variability of assay) when compared with the corresponding pretreatment isolates. However, the vast majority (11) of these pretreatment isolates either had unexpectedly low EC50 levels and/or had post-treatment isolates that lacked any amino acid changes within their reverse transcriptase (RT) gene to account for the observed change in sensitivity. Of the four remaining isolates, two appeared to have a multi-resistant phenotype to several nucleoside analogues and two had no detectable RT amino acid changes to account for the observed change in stavudine sensitivity. To date, clinical HIV-1 isolates displaying stavudine-specific resistance have yet to be reported. Furthermore, full or partial RT sequence analysis of 194 post-treatment isolates failed to identify any consistent amino acid changes. The strain-specific V75T mutation reported to confer stavudine resistance to the HXB2 HIV-1 strain in vitro, was found in only six isolates and did not correlate with stavudine resistance. This low incidence of stavudine resistance is in striking contrast to that observed with other nucleoside analogues and further supports the use of stavudine in first-line combination therapy for HIV patients.
Authors:
P F Lin; C J González; B Griffith; G Friedland; V Calvez; F Ferchal; R F Schinazi; D H Shepp; A B Ashraf; M A Wainberg; V Soriano; J W Mellors; R J Colonno
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Antiviral therapy     Volume:  4     ISSN:  1359-6535     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  1999  
Date Detail:
Created Date:  2000-03-02     Completed Date:  2000-03-02     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  21-8     Citation Subset:  IM; X    
Affiliation:
Bristol-Myers Squibb, Wallingford, Conn., USA. linp@bms.com
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MeSH Terms
Descriptor/Qualifier:
Acquired Immunodeficiency Syndrome / drug therapy*
Anti-HIV Agents / therapeutic use*
Drug Resistance
HIV-1 / drug effects
Humans
Phenotype
RNA-Directed DNA Polymerase / genetics
Stavudine / therapeutic use*
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 3056-17-5/Stavudine; EC 2.7.7.49/RNA-Directed DNA Polymerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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