TABLE 1.
Susceptibility of recombinant HIV-1 strains to integrase strand transfer inhibitors
| HIV-1 strain typea | EC50, nM (fold increase)b |
||
|---|---|---|---|
| RAL | EVG | DTG | |
| WT | 12 ± 1.2 | 2.6 ± 0.5 | 2.5 ± 0.1 |
| Mutant | |||
| I60M | 8.4 ± 0.8 (0.7) | 2.2 ± 0.4 (0.9) | 2.4 ± 0.1 (1.0) |
| V72I | 16 ± 2.9 (1.4) | 2.8 ± 0.2 (1.1) | 2.5 ± 0.3 (1.0) |
| L74F | 18 ± 2.1 (1.5) | 5.5 ± 0.4 (2.3) | 1.1 ± 0.1 (0.4)c |
| V75I | 7.5 ± 0.3 (0.7) | 3.5 ± 0.2 (1.2) | 1.3 ± 0.2 (0.5)c |
| L74F V75I | 66 ± 1.2 (5.5)c,d | 27 ± 3.6 (11)c,d | 0.8 ± 0.1 (0.3)c |
| L74I V75I | 12 ± 2.1 (1.0) | 5.3 ± 0.3 (1.9)c | 1.6 ± 0.1 (0.6)c |
| L74M V75I | 21 ± 3.9 (1.8) | 8.0 ± 0.5 (3.1)c | 1.2 ± 0.1 (0.5)c |
| I60M L74F V75I | 44 ± 8.2 (3.7) | 32 ± 8.8 (12) | 1.2 ± 0.1 (0.5)c |
| V72I L74F V75I | 137 ± 17 (11)c | 45 ± 11 (17) | 1.3 ± 0.2 (0.5)c |
| I60M V72I L74F V75I | 47 ± 1.2 (3.9)c | 38 ± 5.9 (15)c | 0.7 ± 0.1 (0.3)c |
Select L74 mutations in the double and triple mutants have been highlighted for emphasis. In the V75I variants, underlining indicates the L74M or L74I mutation did not have an impact on susceptibility, whereas boldface indicates the L74F mutation increased INSTI resistance.
The data shown are means ± standard deviations from three independent experiments. Values in parentheses are fold increases of the EC50 relative to that in the HIV-1 WT.
Statistical significance was calculated for difference between the WT and mutant using a Student t test with a statistical cutoff of P < 0.02.
Statistical significance was calculated for difference between single (L74F or V75I) and corresponding double mutants using a Student t test with a statistical cutoff of P < 0.02.