Pf. Lin et al., GENOTYPIC AND PHENOTYPIC ANALYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES FROM PATIENTS ON PROLONGED STAVUDINE THERAPY, The Journal of infectious diseases, 170(5), 1994, pp. 1157-1164
Development of stavudine resistance was studied using human immunodefi
ciency virus type 1 isolates from 13 patients treated with stavudine f
or 18-22 months. Drug sensitivity testing on 11 of these pre- and post
therapy isolates identified only 2 posttreatment isolates with decreas
ed stavudine sensitivity (ED(50)s <4-fold higher than the average pret
reatment ED(50)). Genotypic analysis of all 13 pairs of isolates ident
ified multiple mutations in the reverse transcriptase (RT) gene. Howev
er, no genetic basis was identified to account for the observed change
s in stavudine susceptibility. A recombinant virus containing the enti
re RT gene of the posttherapy isolate displaying the greatest resistan
ce remained sensitive to stavudine. Five of the stavudine posttreatmen
t isolates developed resistance (9- to 176-fold) to zidovudine, althou
gh the relationship between stavudine treatment and the appearance of
zidovudine resistance remains unexplained. Analysis of 10 additional p
airs of isolates did not confirm this relationship. The low frequency
and modest degree of change in stavudine sensitivity following prolong
ed treatment is very encouraging.