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. 2000 Nov;44(11):3213-6.
doi: 10.1128/AAC.44.11.3213-3216.2000.

Low level of cross-resistance to amprenavir (141W94) in samples from patients pretreated with other protease inhibitors

B Schmidt  1 , K Korn, B Moschik, C Paatz, K Uberla, H Walter
Affiliations

Low level of cross-resistance to amprenavir (141W94) in samples from patients pretreated with other protease inhibitors

B Schmidt et al. Antimicrob Agents Chemother. 2000 Nov.

Abstract

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.

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Figures

FIG. 1
FIG. 1
(A) Percentage of amprenavir sensitive, intermediately resistant, or highly resistant isolates with respect to the number of PI in the treatment history (indinavir, saquinavir, ritonavir, and nelfinavir). (B) Percentage of amprenavir sensitive, intermediately resistant, or highly resistant isolates with respect to individual PI in the treatment history.
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