TABLE 1.
Initial virus | Drug | Initial concn (nM) | Change(s) at culture day: |
FC at day 56a | Final concn (nM) | |||
---|---|---|---|---|---|---|---|---|
14 | 28 | 42 | 56 | |||||
NL432 (wild type) | DTG | 6.4 | No substitution | No substitution | No substitution | E92Q | 3.1 | 6.4 |
G193E | 3.2 | 6.4 | ||||||
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | No substitution | No substitution | Q148R | N155S/D232N | ND | 32 | |
Q148R | 300 | 800 | ||||||
32 | No substitution | N155H | F121Y | F121Y/D232N | 9.2 | 32 | ||
N155H | N155H | 14 to 22 | 160 | |||||
160 | No replication | No replication | No replication | No replication | ||||
EVG | 6.4 | No substitution | Q148R | Q148R | Q148R | 31 | 32 | |
E138K/Q148R | ND | 160 | ||||||
N155H | N155H | N155H | 1.4 to 18 | 32 | ||||
E92Q/N155H | E92Q/N155H | 2,800 | 160 | |||||
E92Q/N155H/R263K | ND | 800 | ||||||
32 | Q148R | Q148R | Q148R | Q148R | 250 | 160 | ||
T66A | T66A | T66A | 14 to 100 | 160 | ||||
160 | No replication | No replication | No replication | No replication | ||||
E92Q mutant | DTG | 6.4 | E92Q | E92Q | E92Q | E92Q | 2.9 to 4.1 | 6.4 |
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | E92Q | E92Q | E92Q | E92Q | 5.7 to 13 | 32 | |
L74M/E92Q | L74M/E92Q | 26 to 120 | 4,000 | |||||
32 | E92Q | E92Q | E92Q | E92Q | 4.8 to 12 | 32 | ||
L74M/E92Q | L74M/E92Q | 21 to 110 | 4,000 | |||||
160 | E92Q | E92Q | E92Q | E92Q | 14 | 160 | ||
L74M/E92Q | L74M/E92Q | 28 to 38 | 4,000 | |||||
EVG | 6.4 | E92Q | E92Q | E92Q | E92Q | 3.2 to 82 | 160 | |
32 | E92Q | E92Q | E92Q | E92Q | 21 to 102 | 160 | ||
160 | E92Q | E92Q | E92Q | E92Q | 29 to 93 | 160 | ||
N155H mutant | DTG | 6.4 | N155H | N155H | N155H | N155H | 2.0 to 3.9 | 32 |
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | N155H | N155H | N155H | N155H | 22 to 79 | 160 | |
N155H/D232N | G70R/N155H | ND | 800 | |||||
N155H/G163R/D232N | 38 to 54 | 4,000 | ||||||
32 | N155H | N155H | N155H | N155H | 26 to 250 | 160 | ||
S119R/N155H | S119R/N155H | 88 to 180 | 4,000 | |||||
160 | N155H | N155H | N155H | N155H | 25 to 52 | 4,000 | ||
P142T/N155H/G163R | P142T/N155H/G163R | 270 | 800 | |||||
EVG | 6.4 | N155H | N155H | N155H | N155H | 41 to 130 | 160 | |
N155H/S230K | N155H/S230K | ND | 160 | |||||
32 | N155H | N155H | N155H | N155H | 38 to 41 | 160 | ||
N155H/D232N | N155H/D232N | 77 | 800 | |||||
160 | N155H | N155H | N155H | N155H | ND | 800 | ||
G70R/V75I/N155H | N155K/E170K | N155K/E170K | ND | 160 | ||||
G70R/V75I/N155H | G70R/V75I/N155H | ND | 160 | |||||
Y143C mutant | DTG | 6.4 | Y143C | No replication | No replication | No replication | ||
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | Y143C | Y143R | Y143R | Y143R | 11 to 28 | 800 | |
Y143R/G163R | 21 | |||||||
32 | Y143C | Y143R | Y143R | Y143R | 16 to 51 | 4,000 | ||
E92Q/Y143R | 45 | |||||||
160 | Y143C | Y143C | G163R | G163R/E170A | ND | 160 | ||
Y143R mutant | DTG | 6.4 | Y143R | Y143R | Y143R | Y143R | 1.7 | 6.4 |
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | Y143R | Y143R | Y143R | Y143R | ND | 800 | |
32 | Y143R | Y143R | Y143R | Y143R | ND | 800 | ||
160 | Y143R | Y143R | Y143R | L74M/Y143R | 78 | 4,000 | ||
Y143R/N155H | >1,400 | |||||||
Q148K mutant | DTG | 6.4 | E138K/Q148K | E138K/Q148K | E138K/Q148K | E138K/Q148K | 47 to 190 | 32 |
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | Q148K | Q148K | Q148K | Q148K | ND | 160 | |
E138K/Q148K | E138K/Q148K | ND | 4,000 | |||||
32 | Q148K | Q148K | Q148K | Q148K | >510 | 160 | ||
E138K/Q148K | E138K/Q148K | E138K/Q148K | ND | 800 | ||||
160 | Q148K | Q148K | Q148K | Q148K | ND | 160 | ||
E138K | E138K/Q148K | E138K/Q148K | >510 | 800 | ||||
E138K/Q148K | E138K/Q148K | E138K/Q148K | >510 | 4,000 | ||||
EVG | 6.4 | Q148K | Q148K | Q148K | Q148K | 950 to 2,500 | 32 | |
E138K/Q148K | E138K/Q148K | 4,900 to >5,400 | 4,000 | |||||
32 | Q148K | Q148K | Q148K | Q148K | 1,500 to 2,500 | 32 | ||
E138K/Q148K | E138K/Q148K | E138K/Q148K | 2,800 to 4,900 | 4,000 | ||||
160 | Q148K | E138K/Q148K | E138K/Q148K | E138K/Q148K | 3,100 to >5,400 | 800 | ||
Q148R mutant | DTG | 6.4 | Q148R | G140S/Q148R | G140S/Q148R | G140S/Q148R | 16 | 6.4 |
G140S/Q148R/V201I | 39 | 32 | ||||||
E138K/Q148R | E138K/Q148R | E138K/Q148R | E138K/G140S/Q148R | 13 | 6.4 | |||
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | Q148R | Q148R | Q148R | Q148R | 84 to 190 | 160 | |
G140S/Q148R | >510 | 800 | ||||||
G140S/Q148R/V259I | ND | 4,000 | ||||||
32 | Q148R | Q148R | Q148R | Q148R | 190 to 250 | 160 | ||
G140S/Q148R | G140S/Q148R | ND | 4,000 | |||||
160 | Q148R | Q148R | Q148R | Q148R | 220 to 370 | 160 | ||
G140S/Q148R | G140S/Q148R | G140S/Q148R | ND | 4,000 | ||||
L74M/Q148R | L74M/G140S/Q148R | L74M/G140S/Q148R | ND | 4,000 | ||||
EVG | 6.4 | Q148R | Q148R | Q148R | Q148R | 170 to 710 | 160 | |
E138K/Q148R | 720 to 1,500 | 800 | ||||||
32 | Q148R | Q148R | Q148R | Q148R | 470 | 32 | ||
E138K/Q148R | 670 | 160 | ||||||
160 | Q148R | Q148R | Q148R | E138K/Q148R | 1,100 to 1,200 | 4,000 | ||
Q148H mutant | DTG | 6.4 | G140S/Q148H | G140S/Q148H | G140S/Q148H | G140S/Q148H | 4.8 to 8.0 | 6.4 |
T97A/G140S/Q148H | 44 | 32 | ||||||
V75I/E138K/G140S/Q148H/M154I | 46 | 32 | ||||||
32 | No replication | No replication | No replication | No replication | ||||
160 | No replication | No replication | No replication | No replication | ||||
RAL | 6.4 | Q148H | Q148H | Q148H | G140S/Q148H | >510 | 4,000 | |
G140S/Q148H | G140S/Q148H | |||||||
32 | Q148H | Q148H | G140S/Q148H | G140S/Q148H | >510 | 4,000 | ||
G140S/Q148H | ||||||||
160 | Q148H | G140S/Q148H | G140S/Q148H | G140S/Q148H | >510 | 4,000 | ||
G140S/Q148H | ||||||||
EVG | 6.4 | Q148H | Q148H | G140S/Q148H | G140S/Q148H | 520 to >5,400 | 4,000 | |
32 | G140S/Q148H | G140S/Q148H | G140S/Q148H | G140S/Q148H | 2800 to >5,400 | 4,000 | ||
160 | G140S/Q148H | G140S/Q148H | G140S/Q148H | G140S/Q148H | 4,000 to >5,400 | 4,000 |
Data from a single experiment, which was performed in duplicate. ND, not determined, because the low viral titer of the culture supernatant did not provide enough signal to evaluate the EC50.