TABLE 2.
Susceptibilities of selected and recombinant HIV-1 strains to various antiviral compounds evaluated in MT-4 and MOLT-4 cells
| Antiviral compound | Cell | IC50 (μM) (fold resistance) in HIV-1 strainsa
|
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Wild type
|
Passaged 35 times
|
Passaged 40 times
|
Passaged 60 times
|
||||||
| HIV(IIIB) | RIN/IIIB | IIIB/L-708,906(35#) | RIN/L-708,906(35#) | IIIB/L-708,906(40#) | RIN/L-708,906(40#) | IIIB/L-708,906(60#) | RIN/L-708,906(60#) | ||
| IN inhibitors | |||||||||
| L-708,906 | MT-4 | 5.7 ± 4.7 | 5.4 ± 3.9 | 16.6 ± 5.4 (2.9) | 23.8 ± 21.0 (4.4) | 25.0 ± 21.8 (4.4) | 24.1 ± 15.3 (4.5) | >55.9 ± 20.0 (>9.8) | >62.6 ± 0.5 (>11.6) |
| MOLT-4 | 1.1 ± 0.9 | ND | 5.0 ± 2.1 (4.5) | ND | 11.9 ± 0.9 (10.8) | ND | 20.0 ± 7.0 (18.2) | ND | |
| S-1360 | MT-4 | 1.6 ± 0.9 | 3.1 ± 1.6 | 10.5 ± 2.5 (6.6) | 13.3 ± 1.2 (4.3) | 10.8 ± 2.2 (6.8) | 13.3 ± 1.6 (4.3) | 13.6 ± 1.6 (8.5) | 21.7 ± 13.0 (7.0) |
| MOLT-4 | 0.3 ± 0.03 | ND | 3.4 ± 0.7 (11.3) | ND | 8.5 ± 8.4 (28.3) | ND | 7.8 ± 7.0 (26.0) | ND | |
| V-165 | MT-4 | 12.7 ± 6.2 | 10.2 ± 3.7 | 11.5 ± 4.8 (0.9) | 9.3 ± 1.6 (0.9) | 9.4 ± 3.5 (0.7) | 9.2 ± 0.7 (0.9) | 8.2 ± 2.5 (0.6) | 9.7 ± 0.7 (1.0) |
| MOLT-4 | 7.5 ± 2.5 | ND | 16.8 ± 3.5 (2.2) | ND | 16.3 ± 12.4 (1.3) | ND | 15.1 ± 12.4 (2.0) | ND | |
| Entry inhibitor | |||||||||
| AMD3100 | MT-4 | 0.019 ± 0.013 | 0.002 ± 0.002 | 0.012 ± 0.001 (0.6) | 0.001 ± 0.001 (0.5) | 0.008 ± 0.004 (0.4) | 0.001 ± 0.001 (0.5) | 0.012 ± 0.005 (0.6) | 0.002 ± 0.001 (1.0) |
| RT inhibitors | |||||||||
| AZT | MT-4 | 0.001 ± 0.0003 | 0.001 ± 0.0004 | 0.001 ± 0.0005 (1.0) | 0.001 ± 0.0003 (1.0) | 0.001 ± 0.0004 (1.0) | 0.002 ± 0.0005 (2.0) | 0.001 ± 0.0002 (1.0) | 0.001 ± 0.0004 (1.0) |
| Nevirapine | MT-4 | 0.056 ± 0.020 | 0.128 ± 0.063 | 0.049 ± 0.012 (0.9) | ND | 0.034 ± 0.022 (0.6) | ND | 0.034 ± 0.011 (0.6) | ND |
| MOLT-4 | 0.024 | ND | 0.024 (1.0) | ND | 0.052 (2.2) | ND | 0.052 (2.2) | ND | |
| PRO inhibitor | |||||||||
| Ritonavir | MT-4 | 0.041 ± 0.029 | 0.088 ± 0.010 | 0.056 ± 0.011 (1.4) | 0.085 ± 0.023 (1.0) | 0.041 ± 0.024 (1.0) | 0.065 ± 0.031 (0.7) | 0.031 ± 0.019 (0.8) | 0.061 ± 0.025 (0.7) |
a
IC50, 50% inhibitory concentration or concentration required to inhibit the CPE of different HIV strains by 50% in MT-4 cells. Fold increase in the IC50 of the compound against the in vitro-selected HIV-1(IIIB) or recombined selected strain compared to the IC50 of the compound against the parental HIV-1(IIIB) strain or the recombined HIV-1(IIIB) strain, respectively, is shown in parentheses. HIV-1 strain designations were explained in Results. Boldface values indicate reduced susceptibility compared to the susceptibility of the wild-type strain. ND, not determined.