TABLE 3.
| Substitution | Fold resistance to:
|
||
|---|---|---|---|
| Efavirenz | Nevirapine | Delavirdine | |
| Single-amino-acid substitutions | |||
| A98Gd | 5.2 | 6.2 | NDc |
| L100Ia | 24 | 5.3 | 30 |
| K101Ea | 6.9 | 14 | 3.5 |
| K101Q | 5.6 | 3.2 | 6.0 |
| K103N/NL4-3a | 19 | 44 | 24 |
| K103N/HXB2 | 36 | >50 | 68 |
| K103R | 0.6 | 0.9 | 1.0 |
| V106Aa | 3.8 | 120 | 13 |
| V106I | 1.1 | 1.9 | 1.3 |
| V108I | 1.6 | 2.8 | 0.9 |
| E138K | 1.1 | ND | ND |
| Y181Ca | 1.1 | 100 | 33 |
| Y188H | 3.8 | 1.9 | 5.0 |
| Y188Ld | 140 | >1,500 | 17 |
| Y188Ca | 4.0 | 44 | 2.3 |
| G190A | 4.6 | 41 | 0.2 |
| G190Sd | 97 | 290 | 0.7 |
| P225H | 1.2 | 1.7 | 0.4 |
| F227L | 0.9 | 3.1 | ND |
| P236L | 0.60 | 1.7 | 66 |
| Multiple-amino-acid substitutions | |||
| S48T/G190S | 110 | 590 | 0.80 |
| L100I/K103Na | 2,400 | 110 | 870 |
| K101E/K103Na | 210 | 310 | 130 |
| K101Q/K103N | 250 | 136 | 36 |
| K103N/V108I | 84 | 270 | 39 |
| K103N/Y181Ca | 32 | >1,600 | 270 |
| K103N/Y188H | 404 | ND | ND |
| V106I/Y188L | >1,400 | 2,600 | 170 |
| S48T/K103N/G190S | 3,800 | 1,100 | 97 |
| K103N/P225H | 100 | 140 | 11 |
| K103N/F227L | 57 | 260 | 2.0 |
| K103N/V108I/P225H | 625 | 268 | 12 |
a
Designated mutants were constructed in a wild-type NL4-3 background. All other viruses were constructed in a wild-type HXB2 background.
b
The average IC90 of each mutant strain was divided by the corresponding wild-type average to obtain the average fold resistance. The IC90s (in nanomolar units) ± standard deviations of efavirenz, nevirapine, and delavirdine for wild-type HXB2 were as follows: 3.2 ± 0.32; 150 ± 59; and 36 ± 15, respectively. For wild-type NL4-3, the IC90s (in nanomolars) ± standard deviations of efavirenz, nevirapine, and delavirdine were 3.0 ± 1.3, 120 ± 52, and 44 ± 15, respectively.
c
ND, not done.
d
Single-amino-acid substitution which required 2-nucleotide substitution.