TABLE 3.
In vitro antiviral activity of NNRTIs against ETR-selected variants
| Isolatea | Subtype | NNRTI mutation(s) | Mean EC50 ± SDb (fold change) |
||
|---|---|---|---|---|---|
| ETR (nM) | EFV (nM) | NVP (μM) | |||
| BK132 | B | wt | 3.7 ± 0.9 | 3.2 ± 0.4 | 0.04 ± 0.02 |
| BK132* | B | E138K, G190E, H221H/Y | 32 ± 3 (8.7) | 12 ± 4 (3.8) | NDc |
| 6383 | A/G | wt | 4.5 ± 0.7 | 3.5 ± 0.7 | 0.041 ± 0.012 |
| 6383* | A/G | V90I, E138K, V179E, Y181C, M230L. | 430 ± 20 (95.6) | 40 ± 10 (11.4) | >5.0 (>121.9) |
| 6399 | A/G | wt | 1 ± 0.2 | 1.2 ± 0.4 | 0.031 ± 0.001 |
| 6399* | A/G | E138K | 5.1 ± 0.2 (5.1) | 4.4 ± 0.1 (3.7) | 0.21 ± 0.01 (6.7) |
| Mole 03 | C | wt | 1.3 ± 0.4 | 1.5 ± 0.1 | 0.038 ± 0.01 |
| Mole 03* | C | V90I, E138K, V179D, Y181Y/C | 140 ± 20 (107.7) | 4.7 ± 2 (3.1) | >10.0 (>263) |
| BG 05 | C | wt | 3.5 ± 0.1 | 1.5 ± 0.2 | 0.012 ± 0.002 |
| BG 05* | C | E138K, V179F, Y181C, M230L | 490 ± 40 (140) | 16 ± 1 (10.7) | >5.0 (>416) |
a
Asterisks (*) indicate an ETR-selected variant at weeks 25 to 30. As stated in the text, isolate 6383 contained the V90I mutation at the baseline.
b
The values represent means of two or three independent experiments, each performed in duplicate. Drug susceptibility was expressed as fold change in EC50, determined by calculating the ratio of EC50s for selected variants and wt viruses (values in parentheses).
c
ND, not determined.