Table 1.

Susceptibility of nelfinavir-resistant HIV variants to other protease inhibitorsa

Isolate (wk)Genotypic change(s)bEC90(μM) (fold change)
NelfinavirRitonavirIndinavirSaquinavirAmprenavir
219 (13)D30N>D, G52S/G2.50 (93)0.03 (<1)0.04 (1)0.03 (4)0.04 (1)
222 (13)D30N>D1.00 (45)0.01 (<1)0.03 (<1)0.03 (4)0.03 (<1)
204 (12)D30D/N, T74T/A1.90 (5)0.010.040.010.04
211 (16)D30N>D, M36M/I, L63P>L0.60 (60)0.03 (3)0.01 (1)0.10 (1)ND
228 (8) D30N0.20 (10)0.010.030.010.04
228 (12)D30N, M46M>I, A71V>A0.90 (5)0.09 (<1)0.01 (<1)0.10 (<1)ND
  • a HIV was isolated from patient PBMCs at baseline and at various times after initiation of nelfinavir therapy (in weeks). Amino acid substitutions were identified by comparison of matched plasma vRNA samples obtained from patients prior to (baseline) and after initiation of nelfinavir therapy by using the consensus sequence as described in Materials and Methods. EC90s were calculated from dose-response curves as described in Materials and Methods. Fold and change values (in parentheses) were calculated by comparing the EC90 of each drug for isolates cultured after therapy with the EC90 of each drug for the matched isolate cultured at baseline (data not shown). Values are derived from one experiment or are the means of two or more experiments. ND, not determined.

  • b Sequence analysis of amino acid substitutions was semiquantitative, e.g., protease gene sequences from HIV-1 isolate 219 from a patient treated with nelfinavir consists of 70 to 85% aspartic acid (N) and 15 to 30% asparagine (D) at residue 30 and approximately equal amounts of glycine (G) and serine (S) at residue 52.