TABLE 4.
Impact of RT connection domain mutations (N348I and T369I/V) on the NNRTI and ZDV susceptibility of viruses lacking or containing well-characterized RT polymerase domain mutations K103N, Y181C, G190A/S, or L100I
| Mutation(s) in RT | Phenotypic susceptibility data: EC50 fold change (SD)a |
|||
|---|---|---|---|---|
| DLV | EFV | NVP | ZDV | |
| T369I | 5.2 (0.50) | 2.4 (0.40) | 8.4 (0.50) | 2.7 (0.80) |
| T369Vb | 5.5 | 3.1 | 9.2 | 2.1 |
| N348I | 3.4 (0.30) | 1.9 (0.30) | 4.1 (0.10) | 2.4 (0.90) |
| T369I/N348I | 29.8 (1.70) | 8.1 (3.10) | 58.6 (2.20) | 5.4 (1.20) |
| K103N | 75.7 (16.80) | 21.3 (9.50) | 81 (41.4) | 1.1 (0.30) |
| K103N/N348I | >250 (NAc) | 115 (41.2) | >400 (NA) | 2.6 (1) |
| K103N/T369I | >250 (NA) | 164.1 (77.40) | >400 (NA) | 2.3 (0.70) |
| K103N/T369I/N348I | >250 (NA) | >700 (NA) | >400 (NA) | 7.9 (0) |
| Y181C | 44.7 (6.70) | 1.7 (0.10) | 317 (143.8) | 0.3 (0.10) |
| Y181C/N348I | >250 (NA) | 3.2 (0.20) | >400 (NA) | 0.7 (0.10) |
| Y181C/T369I | >250 (NA) | 4 (0.8) | >400 (NA) | 0.9 (0.30) |
| Y181C/T369I/N348I | >250 (NA) | 17 (6.2) | >400 (NA) | 2.2 (0.60) |
| G190A | 0.3 (0.10) | 5.2 (1.50) | 127.7 (30.10) | 1.1 (0.20) |
| G190A/N348Ib | 1.1 | 26.0 | >400 | 2.0 |
| G190A/T369I | 1.2 (0.10) | 33.7 (9) | >400 (NA) | 1.7 (0.20) |
| G190A/T369I/N348I | 5.9 (0.80) | >700 (NA) | >400 (NA) | 4.2 (2.10) |
| G190S | 0.3 (0.04) | 63 (9.9) | 145 (65.1) | 0.8 (0.02) |
| G190S/N348I | 0.9 (0.20) | >700 (NA) | >400 (NA) | 1.7 (0.40) |
| G190S/T369I | 0.6 (0.10) | >700 (NA) | >400 (NA) | 0.7 (0.20) |
| G190S/T369I/N348I | 6.9 (0.30) | >700 (NA) | >400 (NA) | 5.8 (0.30) |
| L100I | 34 (0) | 9 (0.1) | 2.1 (0) | 0.1 (0) |
| L100I/N348I | 90.7 (7.20) | 16 (4.4) | 5.3 (0.60) | 0.3 (0.20) |
| L100I/T369I | 49.7 (9.60) | 13.6 (4.80) | 4.8 (0.50) | 0.2 (0.10) |
| L100I/T369I/N348I | >250 (NA) | 137.7 (50.50) | 56.3 (4.20) | 0.5 (0.20) |
a
The data represent mean fold changes (± standard deviations) obtained from the results of three independent experiments. Changes in phenotypic susceptibility are expressed as the fold change in EC50 based on the EC50 of a drug-susceptible reference virus (EC50 of sample/EC50 of reference).
b
Results are from single experiments testing for these two viruses.
c
NA, standard deviations could not be calculated, as the EC50s were greater than the highest drug concentrations tested.