TABLE 2.
Antiviral activity of GW678248 against HIV-1 containing nonnucleoside reverse transcriptase inhibitor resistance mutations in HeLa-CD4 MAGI assay
| HIV-1 RT mutation(s) | IC50 (nM)a of:
|
||
|---|---|---|---|
| GW678248 | Nevirapine | Efavirenz | |
| None | 0.52 ± 0.4 (33) | 88 ± 49 (17) | 0.80 ± 0.4 (39) |
| L100I | 0.5 ± 0.4 (5) | 500 ± 130 (3) | 21 ± 11 (14) |
| K101E | 0.96 ± 0.07 (3) | 520 ± 130 (3) | 2.5 ± 1.1 (8) |
| K103N | 1.0 ± 0.9 (21) | 5,800 ± 3,600 (9) | 25 ± 13 (41) |
| V106A | 3.4 ± 1.7 (19) | 8,200 ± 3,700 (7) | 1.8 ± 1.1 (29) |
| V106I | 1.1 ± 0.8 (8) | 150 ± 130 (4) | 0.8 ± 0.6 (10) |
| V106M | 1.3 ± 1.9 (7) | 2,900 ± 3,600 (3) | 8.6 ± 4 (7) |
| V108I | 0.9 ± 0.6 (8) | 290 ± 170 (7) | 2.1 ± 1.3 (11) |
| E138K | 1.3 ± 0.7 (5) | 65 ± 42 (6) | 0.86 ± 0.3 (8) |
| Y181C | 0.7 ± 0.5 (21) | 10,300 ± 4,100 (10) | 1.6 ± 1 (23) |
| Y188C | 0.11 ± 0.07 (6) | 2,300 ± 1,300 (10) | 1.4 ± 0.7 (11) |
| Y188L | 21 ± 6 (9) | >10,000 (2) | 240 ± 160 (5) |
| G190A | 0.9 ± 0.3 (9) | 12,000 ± 7,200 (4) | 7.0 ± 3 (13) |
| G190E | 0.7 ± 0.5 (7) | 95 (1) | 1.2 ± 0.6 (4) |
| P225H | 0.3 ± 0.2 (5) | 1,200 (1) | 1.7 ± 0.8 (7) |
| P236L | 1.1 ± 0.4 (5) | 56 ± 13 (2) | 0.8 ± 0.9 (9) |
| K103N, L100I | 1.5 ± 0.8 (7) | 7,900 ± 1,700 (4) | 930 ± 500 (7) |
| K103N, V108I | 0.63 ± 0.2 (6) | 23,000 ± 14,000 (4) | 93 ± 75 (14) |
| K103N, Y181C | 1.4 ± 0.9 (10) | >8,000 (6) | 46 ± 19 (22) |
| K103N, G190A | 4.1 ± 3.0 (11) | >10,000 (3) | 490 ± 230 (11) |
| K103N, P225H | 0.7 ± 0.2 (6) | 9,600 ± 2,100 (3) | 150 ± 110 (14) |
| V106A, Y181C | 0.9 ± 0.5 (6) | >10,000 (5) | 3.1 ± 2.5 (8) |
| V106I, Y181C | 4.9 ± 2.2 (6) | >10,000 (3) | 3.6 ± 1.1 (8) |
| V106I, P236L | 7 ± 5 (5) | NDb | 0.7 ± 0.3 (2) |
| V106I, E138K, P236L | 86 ± 62 (2) | 79 (1) | 2.3 ± 1.2 (3) |
| V108I, Y181C | 0.9 ± 0.5 (7) | >10,000 (3) | 3.1 ± 1.5 (6) |
a
IC50s are means ± standard deviations. Values in parentheses = n.
b
ND, not determined.