TABLE 1.
Resistance of RT mutants and wild type, measured with the d4T-TP or AZT-TP inhibition assay with or without 3.2 mM ATP and by HIV-1 drug susceptibility assaya
| Mutation(s) | D4T
|
AZT
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RT assay without ATP
|
RT assay with 3.2 mM ATP
|
Virus assay (fold resist.) | RT assay without ATP (fold resist.) | RT assay with 3.2 mM ATP (fold resist.) | Virus assay (fold resist.) | |||||||
| Ki (nM) | Km (nM) | Ki/Km | Fold resist. | Ki (nM) | Km (nM) | Ki/Km | Fold resist. | |||||
| HXB2 | 1.0 | 140 | 0.0071 | 1.0 (0.1) | 1.6 | 160 | 0.01 | 1.0 (0.1) | 1.0 | 1.0 (0.1) | 1.0 (0.1) | 1.0 |
| M41L, D67N, K70R, T215Y | 0.4 | 110 | 0.0036 | 0.5 (0.2) | 3.0 | 130 | 0.023 | 2.3 (0.2) | 4.1 (1.3) | 0.7 (0.1) | 10.3 (1.2) | 24.1 (7.7) |
| M41L, D67N, K70R, M184V, T215Y | 0.7 | 110 | 0.0064 | 0.9 (0.3) | 5.1 | 150 | 0.034 | 3.4 (0.4) | 3.7 (1.0) | 0.9 (0.5) | 4.3 (0.5) | 6.4 (1.5) |
| M41L, D67N, K70R, M184V, L210W, | 1.5 | 220 | 0.0068 | 1.0 (0.3) | 6.9 | 250 | 0.028 | 2.8 (0.1) | 4.0 (1.3) | 0.7 (0.1) | 5.5 (1.9) | 12.0 (2.6) |
| R211K, L214F, T215Y, T69S-AG | 1.9 | 130 | 0.015 | 2.1 (0.4) | 6.2 | 120 | 0.051 | 5.1 (0.2) | 6.9 (2.7) | 1.3 (0.2) | 10.5 (2.1) | 7.0 (2.0) |
| M41L, T69S-AG, L210W, R211K, L214F, T215Y | 1.3 | 130 | 0.01 | 1.4 (0.3) | 27.0 | 230 | 0.117 | 11.7 (1.4) | 17.1 (0.6) | 0.9 (0.0) | 15.8 (4.0) | >36 |
| T69S-SG | 3.7 | 240 | 0.015 | 2.1 (0.2) | 6.8 | 230 | 0.03 | 3.0 (0.6) | 4.4 (1.1) | 1.4 (0.4) | 6.7 (1.7) | 8.1 (3.1) |
| M41L, T69S-SG, L210W, R211K, L214F, T215Y | 0.9 | 100 | 0.009 | 1.3 (0.3) | 15.2 | 190 | 0.08 | 8.0 (0.5) | 8.3 (1.8) | ND | ND | >36 |
| V75T | 2.6 | 90 | 0.029 | 4.1 (0.6) | 6.6 | 160 | 0.041 | 4.1 (0.6) | 2.7 (0.4) | 2.8 (0.3) | 2.3 (0.2) | 1.4 (0.3) |
| Q151M | 3.0 | 120 | 0.025 | 3.5 (0.9) | 7.1 | 180 | 0.039 | 3.9 (0.2) | 3.0 (0.8) | 4.0 (0.2) | 3.8 (0.4) | 2.1 (0.4) |
Fold resistance data for AZT and AZT-TP are from reference 16a. The RT d4T-TP and AZT-TP assay fold resistance (fold resist.) values were calculated as the increase of the Ki (d4T-TP or AZT-TP)/Km (BrdUTP) ratio compared to the wild-type (HXB2) corresponding ratio. The virus d4T and AZT assay fold resistance values are based on IC50 relative to wild-type HXB2 virus control. The mean IC50s of d4T and AZT for the wild-type control virus were 1.2 and 0.012 μM, respectively. All values are the averages from at least two separate experiments. Standard errors are indicated in parentheses. ND, not determined.