TABLE 4.
Summary of properties of expanded-spectrum NNRTIsa
| NNRTI | Measured potency
(IC90 [nM])
|
% Free drug in tissue culture medium | Intrinsic (free drug) potency (IC90
[nM])
|
% Free drug in human plasma | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Wild type (HIV-1 RF) | K103N | L100I | K103N-V108I | K103N-P225H | K103N- L100I | Wild type | K103N | K103N-V108I | K103N-P225H | K103N-L100I | |||
| DPC 082 | 2.0 ± 0.2 | 21 ± 9.2 | 5.9 ± 3.8 | 220 ± 140 | 180 ± 29 | 550 ± 400 | 53 | 1.1 | 11 | 117 | 95 | 292 | 3.0 |
| DPC 083 | 2.1 ± 0.8 | 27 ± 11 | 11 ± 6.8 | 90 ± 6.6 | 140 ± 92 | 1,690 ± 160 | 39 | 0.8 | 11 | 35 | 55 | 660 | 2.0 |
| DPC 961 | 2.0 ± 0.7 | 10 ± 3.2 | 13 ± 7.9 | 38 ± 4 | 73 ± 18 | 1,100 ± 160 | 31 | 0.6 | 3.1 | 12 | 23 | 340 | 1.5 |
| DPC 963 | 1.3 ± 0.6 | 11 ± 4.8 | 8.0 ± 5.7 | 34 ± 5.4 | 46 ± 2.2 | 890 ± 90 | 37 | 0.5 | 4.0 | 13 | 17 | 330 | 2.8 |
| Efavirenz | 1.7 ± 0.5 | 64 ± 24 | 120 ± 30 | 240 ± 68 | 310 ± 130 | 7,300 ± 5,000 | 27.2 | 0.5 | 17 | 65 | 84 | 1,990 | 0.21–0.54 |
a
Wild-type virus was assessed in MT-2 cells by oligonucleotide capture of viral RNA after 3 days of infection. K103N single and double mutant variants were used to infect MT-4 cells, and viral p24 antigen levels were measured after 3 days. The amounts of the L100I mutant were assessed in MT-2 cells by determination of the yield of infectious virus progeny by plaque assay. The data represent the means ± standard deviations for two to six independent determinations.