Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy

Development of stavudine resistance was studied using human immunodeficiency virus type 1 isolates from 13 patients treated with stavudine for 18-22 months. Drug sensitivity testing on 11 of these pre- and posttherapy isolates identified only 2 posttreatment isolates with decreased stavudine sensiti...

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Veröffentlicht in:The Journal of infectious diseases 1994-01, Vol.170 (6), p.1157-1164
Hauptverfasser: Lin, Pin-Fang, Samanta, H, Rose, R E, Patick, A K, Trimble, J, Bechtold, C M, Revie, DR, Khan, N C, Federici, ME, Li, Hui
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container_issue 6
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container_title The Journal of infectious diseases
container_volume 170
creator Lin, Pin-Fang
Samanta, H
Rose, R E
Patick, A K
Trimble, J
Bechtold, C M
Revie, DR
Khan, N C
Federici, ME
Li, Hui
description Development of stavudine resistance was studied using human immunodeficiency virus type 1 isolates from 13 patients treated with stavudine for 18-22 months. Drug sensitivity testing on 11 of these pre- and posttherapy isolates identified only 2 posttreatment isolates with decreased stavudine sensitivity (ED sub(50)s
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Drug sensitivity testing on 11 of these pre- and posttherapy isolates identified only 2 posttreatment isolates with decreased stavudine sensitivity (ED sub(50)s &lt;4-fold higher than the average pretreatment ED sub(50)). Genotypic analysis of all 13 pairs of isolates identified multiple mutations in the reverse transcriptase (RT) gene. However, no genetic basis was identified to account for the observed changes in stavudine susceptibility. A recombinant virus containing the entire RT gene of the posttherapy isolate displaying the greatest resistance remained sensitive to stavudine. Five of the stavudine posttreatment isolates developed resistance (9- to 176-fold) to zidovudine, although the relationship between stavudine treatment and the appearance of zidovudine resistance remains unexplained. Analysis of 10 additional pairs of isolates did not confirm this relationship. The low frequency and modest degree of change in stavudine sensitivity following prolonged treatment is very encouraging.</description><identifier>ISSN: 0022-1899</identifier><language>eng</language><subject>human immunodeficiency virus</subject><ispartof>The Journal of infectious diseases, 1994-01, Vol.170 (6), p.1157-1164</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids></links><search><creatorcontrib>Lin, Pin-Fang</creatorcontrib><creatorcontrib>Samanta, H</creatorcontrib><creatorcontrib>Rose, R E</creatorcontrib><creatorcontrib>Patick, A K</creatorcontrib><creatorcontrib>Trimble, J</creatorcontrib><creatorcontrib>Bechtold, C M</creatorcontrib><creatorcontrib>Revie, DR</creatorcontrib><creatorcontrib>Khan, N C</creatorcontrib><creatorcontrib>Federici, ME</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><title>Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy</title><title>The Journal of infectious diseases</title><description>Development of stavudine resistance was studied using human immunodeficiency virus type 1 isolates from 13 patients treated with stavudine for 18-22 months. 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subjects human immunodeficiency virus
title Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy
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