TABLE 5.
Evaluation of BMS-955176 toward viruses resistant to other classes of antiretroviralsa
| ARV | Class | Fold change in EC50 (SD) relative to parental strain |
|||||
|---|---|---|---|---|---|---|---|
| NRTI (184V) | NRTI (41L, 67N, 215F, 219E, 69N)b | NNRTI (103N, 181C) | PI (46I, 82F, 84V, 90 M)c | PI (54V, 82A, 84V 84V)d | INI (140S, 148H) | ||
| BMS-955176 | MI | 1.1 (0.29) | 1.88 (0.21) | 1.0 (0.20) | 0.94 (0.24) | 1.4 | 0.66 (0.18) |
| Lamivudine | NRTI | >60 (59) | 6.8 (3.9) | 1.07 (0.24) | 1.28 (0.02) | ND | 1.4 (0.11) |
| Zidovudine | NRTI | 0.78 (0.03) | 79 (5) | 1.03 (0.17) | 1.56 (0.46) | ND | 0.82 (0.41) |
| Nevirapine | NNRTI | 1.3 (0.2) | 1.6 (0.2) | >131 (108) | 0.83 (0.08) | ND | 0.89 (0.59) |
| Efavirenz | NNRTI | 1.0 (0.1) | ND | 55 (2.2) | 0.20 (0.01) | 1.4 | 0.60 (0.3) |
| Rilpivirine | NNRTI | 2.0 (0.3) | ND | 8.1 (1.5) | 2.6 (0.8) | ND | 1.0 (0.5) |
| Darunavir | PI | 1.2 (0.4) | ND | 0.90 (0.1) | 41 (1.9) | 2.3 | 1.1 (0.1) |
| Atazanavir | PI | 1.1 (0.1) | 2.27 (0.02) | 0.93 (0.03) | 38c | 39 | 1.0 (0.21) |
| Raltegravir | INI | 1.9 (0.6) | ND | 1.8 (0.4) | 0.18 (0.07) | ND | >340 (72) |
a
Values are means (SD) of experiments performed a minimum of 3 times. ND, not determined. Boldface indicates fold change in EC50 > 6.8.
b
AZT-resistant virus 7324-1.
c
See the work of Gong et al. (41).
d
gag/pr gene from PI-resistant virus (provided by Monique Nijhuis), transferred to an NLRepRluc backbone.