Table 2.
Breakthrough of wild-type HIV-1(IIIB) and 184-Ile mutant HIV-1 and 184-Val mutant HIV-1 strains in CEM cell cultures in the presence of a variety of NNRTIs
| Compound | Initial concentration, μg/ml | Wild-type HIV-1
|
184-Ile mutant
HIV-1
|
184-Val mutant HIV-1
|
|||
|---|---|---|---|---|---|---|---|
| Virus breakthrough*† | Mutations in the RT | Virus breakthrough*† | Mutations in the RT | Virus breakthrough*† | Mutations in the RT | ||
| Pyridinone L-697661 | 0.05 | 5 (3) | ND | 5 (3) | ND | 3 (3) | ND |
| 0.25 | 5 (3) | None | 5 (3) | 184-Ile | 5 (3) | 184-Val | |
| Nevirapine | 0.1 | 7 (7) | ND | 5 (5) | ND | 5 (5) | ND |
| 0.5 | 20 (14) | 106-Ala | 9 (7) | 184-Ile | 23 (11) | 184-Val + 188-Cys/WT(Tyr) + 190-Ala/WT(Gly) | |
| BHAP U-90152 | 0.1 | 23 (11) | 236-Leu | 7 (7) | ND | 17 (11) | 184-Val + 236-Leu |
| 0.5 | —‡ | NA‡ | 15 (11) | 184-Ile + 188-His | 34 (32) | 184-Val + 236-Leu | |
| 8-chloro-TIBO | 0.025 | 25 (18) | 101-Glu | 9 (7) | ND | 27 (18) | 184-Val + 106-Ala |
| 0.1 | — | NA | 13 (7) | 184-Ile + 188-His | 30 (25) | 184-Val + 106-Ile | |
| α-APA (Loviride) | 0.025 | 16 (7) | ND | 5 (3) | ND | 13 (7) | ND |
| 0.1 | 23 (11) | 181-Cys | 13 (7) | 184-Ile + 188-His | 23 (18) | 184-Val + 181-Cys | |
| Quinoxaline HBY 097 | 0.005 | 33 (21) | 101-Glu | 13 (7) | 184-Ile + 188-His | — | NA |
| 0.02 | — | NA | 20 (11) | 184-Ile + 188-His | — | NA | |
| TSAO-m3T | 0.1 | 9 (3) | ND | 5 (3) | ND | 5 (3) | ND |
| 0.5 | 16 (11) | 138-Lys | 9 (7) | 184-Ile | 13 (7) | 184-Val + 138-Lys/WT(Glu) | |
| Thiocarboxanilide UC-10 | 0.1 | 20 (11) | 179-Asp | 9 (7) | ND | 18 (7) | 184-Val + 101-Arg/WT(Lys) + 103-Asn/WT(Lys) |
| 0.5 | — | NA | 20 (11) | 184-Ile + 188-His | — | NA | |
| Thiocarboxanilide UC-781 | 0.01 | 20 (11) | 106-Ala/WT(Val) | 11 (7) | 184-Ile + 188-His | 18 (14) | 184-Val + 181-Cys |
| 0.05 | — | NA | 18 (11) | 184-Ile + 188-His | — | NA | |
| MKC-442 (I-EBU) | 0.05 | 23 (11) | 181-Cys | 9 (7) | ND | 25 (14) | 184-Val + 188-His |
| 0.25 | — | NA | 13 (7) | 184-Ile + 188-His§ | 48 (35) | 184-Val + 188-His | |
ND, not determined; NA, not applicable.
*
Data indicate the mean day required for 50% cytopathicity to develop (after initiation of the experiment).
†
Values in parentheses represent the first day of microscopically visible virus breakthrough.
‡
Virus breakthrough was completely suppressed in the presence of the drugs, even after further subcultivation of the cell cultures in the absence of the drugs.
§
This virus strain was also shown to contain a 204-Asp mutation in its RT.