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Antimicrobial Agents and Chemotherapy, November 2000, p. 3213-3216, Vol. 44, No. 11
Institute of Clinical and Molecular Virology,
German National Reference Centre for Retroviruses, University of
Erlangen-Nürnberg, Erlangen,1 and
Institute of Virology, University of Leipzig,
Leipzig,2 Germany
Received 20 December 1999/Returned for modification 7 April
2000/Accepted 31 July 2000
The therapeutic success of an antiretroviral salvage regimen
containing protease inhibitors (PI) is limited by PI-resistant viral
strains exhibiting various degrees of resistance and cross-resistance. To evaluate the extent of cross-resistance to the new PI amprenavir, 155 samples from 132 human immunodeficiency virus type 1-infected patients were analyzed for viral genotype by direct sequencing of the
protease gene. Concomitantly, drug sensitivity to indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir was analyzed by a
recombinant virus assay. A total of 111 patients had been pretreated
with 1-4 PI, but all were naive to amprenavir. A total of 105 samples
(67.7%) were sensitive to amprenavir; 25 samples (16.1%) were
intermediately resistant, and another 25 samples were highly resistant
(4- to 8-fold- and >8-fold-reduced sensitivity, respectively). The
mutations 46I/L, 54L/V, 84V, and 90M showed the strongest association
with amprenavir resistance (P < 0.0001). The scoring
system using 84V and/or any two of a number of mutations (10I/R/V/F,
46I/L, 54L/V, and 90M) predicted amprenavir resistance with a
sensitivity of 86.0% and a specificity of 81.0% within the analyzed
group of samples. Of 62 samples with resistance against 4 PI, 23 (37.1%) were still sensitive to amprenavir. In
comparison, only 2 of 23 samples (8.7%) from nelfinavir-naive
patients with resistance against indinavir, saquinavir, and ritonavir
were still sensitive to nelfinavir. Amprenavir thus appears to be an
interesting alternative for PI salvage therapy.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Low Level of Cross-Resistance to Amprenavir (141W94) in Samples
from Patients Pretreated with Other Protease Inhibitors
*
Corresponding author. Mailing address: Institute of
Clinical and Molecular Virology, German National Reference Centre for Retroviruses, University of Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany. Phone: 49-9131-85-24010. Fax:
49-9131-85-26485. E-mail:
baschmid{at}viro.med.uni-erlangen.de.
Antimicrobial Agents and Chemotherapy, November 2000, p. 3213-3216, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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