TABLE 3.
Changes in EC50 values (relative to wt EC50) of VRX-413638 and efavirenz against clinical HIV-1 isolates containing both NRTI and NNRTI resistance mutationsa
| NRTI mutation(s) | NNRTI mutation(s) | Mean change (fold) in EC50
|
|
|---|---|---|---|
| VRX-413638 (wt EC50 = 36 nM) | Efavirenz (wt EC50 = 1.0 nM) | ||
| L74V | V106A, F227L | 0.4 | 630 |
| M41L, D67N, T69N, L74V, M184V, L210W, T215Y, K219E | K101P, Y188L, F227L | 0.4 | >2,500 |
| L210W, K219E | K101E, Y181C, G190A | 1.1 | 328 |
| M41L, D67N, T69N, L210W, T215Y | K103N, G190A | 1.3 | 443 |
| M41L, D67N, T69N, L74V, M184V, L210W, T215Y, K219E | L100I, K103N | 1.4 | >2,500 |
| M41L, T69N, L210W, T215Y | K103N, Y181V | 1.5 | 19 |
| M41L, D67N, L74V, M184V, L210W, T215Y, K219E | K101H, Y181C, G190S | 1.7 | >2,500 |
| M41L, D67N, T69N, V75I, M184V, L210W, T215Y, K219E | K101E, K103N, V108I | 2 | 1,912 |
| D67N, K70R, K219E | V106I, V108I, Y181C | 2.2 | 7 |
| M184V, T215Y | Y188L | 2.7 | 106 |
| D67N, T69N, K70R, M184V, T215Y, K219E | K103N | 3.3 | 34 |
| M41L, A62V, V75I, M184V, T215Y | K103N, V108I | 4.4 | 196 |
| D67N, K70R, M184V, T215Y, K219E | Y188L, G190A | 5.2 | 2,385 |
| L74V, M184V | K103N, V106A, F227L | 8 | 685 |
| M41L, A62V, M184V, T215Y, K219E | K101Q, V106A | 8.2 | 3 |
a
EC50 values were determined at Monogram Biosciences, Inc., using the company's PhenoScreen test. Replicate assays were not performed, so the SD is not available.