TABLE 3.
Median fold changes in IC50 against viral isolates containing mutations associated with reduced in vitro susceptibility to lopinavir
Mutation | Isolates containing mutation
|
Isolates lacking mutation
|
Pa by:
|
|||||
---|---|---|---|---|---|---|---|---|
n | Fold IC50
|
n | Fold IC50
|
|||||
Median | Mean | Median | Mean | Wilcoxon | ANOVA | |||
L10F/I/R/V | 69 | 4.6 | 14.5 | 43 | 0.9 | 1.4 | <0.0001 | <0.0001 |
K20M/R | 14 | 30.5 | 29.3 | 98 | 1.6 | 6.6 | 0.0001 | <0.0001 |
L24I | 10 | 14.0 | 26.7 | 102 | 1.7 | 7.8 | 0.0011 | 0.0008 |
M46I/L | 41 | 4.2 | 15.8 | 71 | 1.1 | 5.8 | 0.0003 | 0.0002 |
F53L | 13 | 4.6 | 24.6 | 99 | 1.6 | 7.5 | 0.0019 | 0.0014 |
I54L/T/V | 38 | 16.0 | 23.7 | 74 | 1.1 | 2.1 | <0.0001 | <0.0001 |
L63P | 88 | 2.5 | 11.5 | 24 | 1.1 | 2.1 | 0.0026 | 0.0023 |
A71I/L/V/RT | 65 | 3.6 | 11.2 | 47 | 1.1 | 7.1 | 0.0002 | 0.0001 |
V82A/F/T | 40 | 14.0 | 21.5 | 72 | 1.1 | 2.8 | <0.0001 | <0.0001 |
I84V | 19 | 6.1 | 14.8 | 93 | 1.4 | 8.4 | 0.0007 | 0.0004 |
L90M | 48 | 3.4 | 12.4 | 64 | 1.1 | 7.3 | 0.0004 | 0.0003 |
Since the M97-765 (Virco) and M98-957 (ViroLogic) baseline isolates were analyzed using different single-cycle phenotypic assays, a sensitivity analysis that introduced a twofold discordance between the assays was performed. A twofold discordance in one direction did not affect which mutations were statistically significant using the Wilcoxon rank sum test and produced only a minor change in the outcome of the confirmatory analysis (ANOVA), wherein the L63P mutation changed from statistically to marginally significant. A twofold discordance in the other direction did not affect the statistical significance of any of the 11 mutations but produced an apparent statistically significant association of the G73A/S/T mutation.