Table 6. Mutations and polymorphisms in samples genotyped under LPV/r treatment.
Samples failing LPV/r as first PI n = 114 | Samples failing LPV/r as second or higher PI n = 126 | p | ||||||||||||||||||||
B n = 22 | C n = 67 | nonBC n = 25 | B n = 21 | C n = 89 | non-BC n = 13 | LPV/r first PI | LPV/r second or higher PI | First vs. second or higher | ||||||||||||||
Samples revealing major PI mutations | 0 | 7 (10%) | 1 (4%) | 10 (47.6%) | 40 (44.9%) | 8 (61.5%) | B vs. C | B vs. non-BC | C vs. non-BC | B vs. C | B vs. non-BC | C vs. non-BC | B | C | non-BC | |||||||
PI Mutations | No | % | No | % | No | % | No | % | No | % | No | % | ||||||||||
I | L10F/I/V | 2 | 9 | 8 | 12 | 6 | 24 | 11 | 52 | 36 | 40 | 6 | 46 | 0.003 | <0.00001 | |||||||
G16E | 0 | 0 | 9 | 13 | 2 | 8 | 0 | 0 | 8 | 9 | 0 | 0 | 0.1 | |||||||||
K20R/I/M/T | 3 | 14 | 15 | 22 | 9 | 36 | 3 | 14 | 38 | 43 | 7 | 54 | 0.1 | 0.02 | 0.02 | 0.01 | ||||||
L24I | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 5 | 3 | 3 | 3 | 23 | 0.03 | 0.03 | ||||||||
L33F | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 10 | 8 | 9 | 2 | 15 | 0.01 | |||||||||
M36I | 4 | 18 | 64 | 96 | 22 | 88 | 8 | 38 | 88 | 99 | 10 | 77 | <0.00001 | <0.00001 | <0.00001 | 0.04 | 0.006 | |||||
K43T | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | ||||||||||
M46I/L | 0 | 0 | 4 | 6 | 1 | 4 | 6 | 29 | 23 | 26 | 3 | 23 | 0.009 | 0.001 | 0.1 | |||||||
I47A/V | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | ||||||||||
G48V/M | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 5 | 1 | 1 | 2 | 15 | 0.04 | |||||||||
I50V/L | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 8 | ||||||||||
F53L | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 5 | 1 | 1 | 2 | 15 | 0.04 | |||||||||
I54A/V | 0 | 0 | 4 | 6 | 1 | 4 | 6 | 29 | 28 | 31 | 6 | 46 | 0.009 | <0.00001 | 0.004 | |||||||
Q58E | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 1 | 8 | ||||||||||
L63P | 12 | 55 | 23 | 34 | 11 | 44 | 16 | 76 | 37 | 42 | 10 | 77 | 0.007 | 0.01 | 0.03 | 0.1 | 0.09 | |||||
A71V | 3 | 14 | 2 | 3 | 1 | 4 | 6 | 29 | 15 | 17 | 3 | 23 | 0.09 | 0.008 | 0.1 | |||||||
G73A/C/S/T | 0 | 0 | 1 | 1 | 0 | 0 | 2 | 10 | 2 | 2 | 1 | 8 | ||||||||||
T74P/S | 0 | 0 | 7 | 10 | 1 | 4 | 0 | 0 | 26 | 29 | 0 | 0 | 0.002 | 0.003 | 0.04 | 0.005 | ||||||
L76V | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 5 | 7 | 8 | 2 | 15 | 0.1 | 0.1 | ||||||||
V82A/C/S | 0 | 0 | 6 | 9 | 1 | 4 | 3 | 14 | 26 | 29 | 6 | 46 | 0.002 | 0.06 | 0.1 | 0.002 | 0.004 | |||||
I84V | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 19 | 4 | 4 | 2 | 15 | 0.04 | 0.07 | <0.05 | 0.1 | 0.1 | |||||
L89V | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 3 | 3 | 0 | 0 | ||||||||||
L90M | 0 | 0 | 1 | 1 | 0 | 0 | 6 | 29 | 18 | 20 | 1 | 8 | 0.009 | <0.00001 | ||||||||
II | V11I | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 5 | 1 | 1 | 0 | 0 | |||||||||
I13V | 4 | 18 | 2 | 3 | 11 | 44 | 8 | 38 | 10 | 11 | 3 | 23 | 0.03 | 0.07 | <0.00001 | 0.006 | 0.07 | |||||
L23I | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 8 | ||||||||||
D30N | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | ||||||||||
D60E | 0 | 0 | 5 | 7 | 3 | 12 | 3 | 14 | 3 | 3 | 4 | 31 | 0.08 | 0.005 | 0.1 | |||||||
I62V | 14 | 64 | 5 | 7 | 4 | 16 | 9 | 43 | 13 | 15 | 4 | 31 | <0.00001 | 0.001 | 0.01 | |||||||
H69K/Q/R/N | 2 | 9 | 67 | 100 | 20 | 80 | 5 | 24 | 89 | 100 | 7 | 54 | <0.00001 | <0.00001 | 0.001 | <0.00001 | <0.00001 | 0.1 | ||||
V77I | 7 | 32 | 2 | 3 | 1 | 4 | 7 | 33 | 1 | 1 | 3 | 23 | 0.001 | 0.02 | <0.00001 | 0.006 | 0.1 | |||||
N83D | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | ||||||||||
I85V | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 5 | 6 | 0 | 0 | ||||||||||
N88D/S | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 10 | 4 | 4 | 0 | 0 | 0.1 | |||||||||
I93L | 6 | 27 | 67 | 100 | 12 | 48 | 10 | 48 | 87 | 98 | 5 | 38 | <0.00001 | <0.00001 | <0.00001 | <0.00001 | <0.00001 | |||||
III | T12S | 0 | 0 | 13 | 19 | 1 | 4 | 2 | 10 | 22 | 25 | 0 | 0 | 0.03 | 0.01 | 0.08 | ||||||
I15V | 2 | 9 | 29 | 43 | 3 | 12 | 2 | 10 | 57 | 64 | 4 | 31 | 0.004 | <0.00001 | 0.006 | <0.00001 | 0.03 | 0.01 | ||||
L19I/K/M/T/V | 1 | 5 | 18 | 27 | 2 | 8 | 3 | 14 | 30 | 34 | 3 | 23 | 0.03 | 0.01 | 0.09 | 0.1 | ||||||
E35D | 10 | 45 | 6 | 9 | 15 | 60 | 4 | 19 | 16 | 18 | 6 | 46 | <0.0001 | 0.01 | <0.0001 | 0.03 | 0.1 | |||||
S37N | 4 | 18 | 29 | 43 | 9 | 36 | 6 | 29 | 51 | 57 | 8 | 62 | 0.04 | 0.03 | 0.08 | 0.1 | ||||||
R41K | 3 | 14 | 64 | 96 | 21 | 84 | 4 | 19 | 85 | 96 | 8 | 62 | <0.00001 | <0.00001 | 0.08 | <0.00001 | 0.03 | 0.001 |
Samples from 237 patients under LPV/r treatment were analyzed. The last available sample from each patient was used. Mutations were divided into three groups according to: I - amino-acids that appear in at least one algorithm for LPV/r resistance (reviewed in [39]); II - other amino-acids known to be involved in resistance to PI; III - amino-acids that are not known to be involved in resistance to PI for which a statistically significant difference between subtypes was found. Amino acids that appear in all four algorithms are shown in bold type and those that appear in 3 different algorithms in italics. For mutation that are significantly different between subtypes the most prevalent variant is shown in bold type. In order to emphasize significant differences only p values smaller than 0.1 were noted. Mutations V32I, E34Q (Group I) and E35G (Group II) did not appear at all and were taken out from the table.
B – subtype B; C – subtype C; LPV/r – Lopinavir/ritonavir; non-BC– subtypes other than B or C; PI – protease Inhibitor.