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

The therapeutic success of an antiretroviral salvage regimen containing pro tease inhibitors (PI) is limited by PI-resistant viral strains exhibiting v arious degrees of resistance and cross-resistance. To evaluate the extent o f cross-resistance to the new PI amprenavir, 155 samples from 132 human imm unodeficiency virus type 1-infected patients were analyzed for viral genoty pe by direct sequencing of the protease gene. Concomitantly, drug sensitivi ty to indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir was anal yzed by a recombinant virus assay. A total of 111 patients had been pretrea ted 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, 84 V, 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 mutati ons (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 grou p of samples. Of 62 samples with resistance against 4 PI, 23 (37.1%) were s till sensitive to amprenavir. In comparison, only 2 of 23 samples (8.7%) fr om 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.