Table 1. Effects of mutations in HIV-1 RNase H on sensitivity to RT inhibitors.
AZT
|
d4T
|
ddI
|
3TC
|
EFV
|
||||||
---|---|---|---|---|---|---|---|---|---|---|
IC50 ± SE, μM | Fold inc. | IC50 ± SE, μM | Fold inc. | IC50 ± SE, μM | Fold inc. | IC50 ± SE, μM | Fold inc. | IC50 ± SE, μM | Fold inc. | |
Wild type | 0.04 ± 0.004* | - | 0.45 ± 0.04* | - | 10.99 ± 1.94† | - | 5.23 ± 0.98† | - | 1.4 ± 0.33† | - |
AZT-R | 0.99 ± 0.36‡ | 23 | 1.08 ± 0.17‡ | 2.4 | 10.87 ± 2.7†§ | None | >20† | >3.8 | 1.2 ± 0.16†§ | None |
D549N | 0.52 ± 0.15† | 12 | 1.06 ± 0.24‡ | 2.4 | 20.78 ± 2.76‡ | 1.9 | 8.85 ± 2.9†§ | None | 0.99 ± 0.3†§ | None |
H539N | 7.96 ± 1.69† | 185 | 4.51 ± 0.22† | 10 | ND | ND | ND | |||
AZT-R+D549N | ≈50‡¶ | ≈1,250 | 5.62 ± 1.55‡ | 12.5 | 9.94∥ | None | >20∥ | >3.8 | 0.89∥ | None |
WT+E478Q mixed virions | 0.22 ± 0.07† | 5.5 | 1.6 ± 0.6† | 3.6 | ND | ND | ND |
IC50 means and standard errors were calculated by using sigmaplot 8.0 as described in Methods. Fold increases (Fold inc.) were calculated only for statistically significant differences in IC50 (P < 0.05, relative to wild type) by dividing the mutant virus IC50 mean by the wild-type virus IC50 mean for each drug. All infections were performed in duplicate, and the results were averaged. ND, not determined; -, not applicable.
IC50 mean calculated based on measurements of 9-15 separate infections
IC50 mean calculated based on measurements of two to four separate infections
IC50 mean calculated based on measurements of five to seven separate infections
IC50 is not statistically different from the wild type (P > 0.03)
For four of the five experiments, the highest drug concentration tested (10 μM) inhibited viral replication only by 10-30%; in one experiment, 50 μM AZT inhibited viral replication by 52%
IC50 mean calculated based on measurements of one infection