Table 2.

Susceptibility of HIV-1 variants to nelfinavir and other protease inhibitors

HIV-1 NL4-3 variant(s)bEC90(μM) (fold change) with the following compoundsa:
NelfinavirRitonavirIndinavirSaquinavirAmprenavir
HIV-1 NL4-30.030.050.060.030.08
p22 (D30N/A71V)0.19 (6)0.090.070.010.04
p28 (M46I/I84V)0.83 (28)0.90 (18)0.78 (13)0.16 (5)ND
D30N0.18 (6)0.010.010.010.02
N88D0.020.010.010.030.02
I84V0.13 (4)0.80 (16)0.64 (11)0.09 (3)ND
D30N/N88D0.18 (6)0.010.010.010.04
D30N/A71V0.92 (31)0.010.040.010.02
D30N/M46I/A71V0.92 (31)0.040.040.010.04
  • a Values in parentheses were calculated by comparing the EC90s of wild-type HIV-1 NL4-3 and variant HIV-1 NL4-3 strains as determined in susceptibility assays with MT-4 cells as described in Materials and Methods. Fold changes (≥threefold) in EC90s are indicated. Variant HIV-1 NL4-3 strains and wild-type HIV-1 NL4-3 were analyzed in parallel for sensitivity to all inhibitors tested. Values are derived from one experiment or are the means of two or more experiments. ND, not determined.

  • b Virus strains. HIV-1 NL4-3 represent wild-type HIV-1; p22 and p28 variants are HIV-1 NL4-3 strains isolated following 22 and 28 serial passages, respectively (35); D30N, N88D, I84V, D30N/N88D, D30N/A71V, and D30N/M46I/A71V represent recombinant HIV-1 NL4-3 strains containing HIV protease genes which were modified by oligonucleotide-mediated, site-directed mutagenesis to contain the indicated substitutions.