TABLE 5.
Influence of RT connection domain mutations (N348I and T369I) on NNRTI and ZDV susceptibility in patient-derived viruses containing well-known NNRTI and NRTI resistance mutations in the RT polymerase domain
| Patient sample (mutation[s] in RT) + C terminus RT mutations | Phenotypic susceptibility data: EC50 fold change (SD)a |
|||
|---|---|---|---|---|
| DLV | EFV | NVP | ZDV | |
| 50 (K103N) | 63.3 (12.60) | 22.3 (3.80) | 65.3 (7.51) | 1.0 (0.20) |
| 50 + T369I | >250 (NAb) | >700 (NA) | >400 (NA) | 3.3 (1.30) |
| 50 + N348I | >250 (NA) | >700 (NA) | >400 (NA) | 2.7 (1) |
| 58 (M41L, K103N, V118I, Y181Y/C, G190G/A, L210W, T215Y) | 128 (19.3) | 23.7 (3.20) | >400 (NA) | 643.7 (140.6) |
| 58 + T369I | >250 (NA) | >700 (NA) | >400 (NA) | >2,400 (NA) |
| 58 + N348I | >250 (NA) | >700 (NA) | >400 (NA) | >2,400 (NA) |
| 62 (K103N, M184V, T215Y) | 12.7 (3.10) | 17.7 (2.50) | 55.7 (9.71) | 2.0 (0.14) |
| 62 + T369I | 112 (16) | 146.7 (91.60) | >400 (NA) | 11.8 (2) |
| 62 + N348I | 79.7 (4.50) | 93 (26.1) | >400 (NA) | 7.1 (2.30) |
| 45 (M41L, D67N, V118I, M184M/V, L210W, T215Y) | 0.1 (0.02) | 0.17 (0.06) | 0.3 (0.01) | 89.7 (14.50) |
| 45 + T369I | 0.3 (0.03) | 0.6 (0.06) | 2.1 (0.01) | >2,400 (NA) |
| 45 + N348I | 0.2 (0.02) | 0.47 (0.06) | 0.81 (0.11) | >2,400 (NA) |
a
The data shown 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
NA, standard deviations could not be calculated as the EC50s were greater than the highest drug concentrations tested.