Table 2. In vitro activity of PA-457 against drug-resistant virus isolates.
| Resistance, IC50, nM
|
||||||
|---|---|---|---|---|---|---|
| Virus | Phenotype | Genotype | PA-457 | AZT | Nev | Ind |
| N119* | NNRTI | Y181C | 5.1 | — | >3,800 (>570×) | — |
| A17* | NNRTI | K103N/Y181C | 5.4 | — | 3,000 (450×) | — |
| RF/41-D2* | PI | V82A | 9.8 | — | — | 28.0 (4×) |
| RF/L/323-9-1* | PI | I84V | 5.8 | — | — | 25.9 (4×) |
| M461/L63P V82T/I84V† | PI | M46I/L63P/V82T/I84V | 12.8 | — | — | 101.9 (12×) |
| 1495-2† | NRTI | K70R/T215Y/F | 2.7 | 29.4 (7×) | — | — |
| G910-11† | NRTI | T215Y/F | 13.3 | 216.0 (50×) | — | — |
Control compounds included zidovudine (AZT), nevirapine (Nev), and indinavir (Ind). Changes in activity from WT for drugs against resistant virus isolates are shown in parentheses.
*
Assays used MT 2 cell line targets and cell killing as an endpoint for virus replication.
†
Assays were carried out in a manner identical to that for clinical isolates.