Table 7.
Antiviral activities of 11 against laboratory PI‐resistant HIV‐1 variants.
|
Virus |
EC50 [μm] of drug[a] |
||||||||
|---|---|---|---|---|---|---|---|---|---|
|
SQV |
RTV |
IDV |
NFV |
APV |
LPV |
ATV |
DRV |
11 (GRL‐98065) |
|
|
HIV‐1NL4‐3 |
0.007 |
0.033 |
0.034 |
0.033 |
0.026 |
0.031 |
0.0042 |
0.0030 |
0.0003 |
|
HIV‐1SQV 5μm |
>1 (>143) |
>1 (>30) |
>1 (>29) |
0.48 (15) |
0.33 (13) |
0.27 (9) |
0.326 (78) |
0.0058 (2) |
0.006 (20) |
|
HIV‐1RTV 5μm |
0.010 (1) |
>1 (>30) |
0.25 (7) |
0.21 (6) |
0.28 (11) |
0.16 (5) |
0.018 (4) |
0.018 (6) |
0.0025 (8) |
|
HIV‐1IDV 5μm |
0.059 (8) |
>1 (>30) |
>1 (>29) |
0.47 (14) |
0.17 (7) |
0.26 (8) |
0.06 (14) |
0.015 (5) |
0.0037 (12) |
|
HIV‐1NFV 5μm |
0.024 (3) |
0.051 (2) |
0.27 (8) |
>1 (>30) |
0.060 (2) |
0.024 (1) |
0.021 (5) |
0.0033 (1) |
0.0024 (8) |
|
HIV‐1APV 5μm |
0.031 (4) |
0.29 (9) |
0.200 (6) |
0.27 (8) |
>1 (>38) |
0.23 (7) |
0.003 (1) |
0.33 (110) |
0.032 (107) |
|
HIV‐1LPV 1μm |
0.032 (5) |
>1 (>30) |
>1 (>29) |
0.49 (15) |
0.31 (12) |
0.31 (10) |
0.040 (10) |
n.d. |
0.0075 (25) |
|
HIV‐1ATV 1μm |
0.037 (5) |
0.12 (4) |
0.388 (11) |
0.22 (7) |
0.20 (8) |
0.033 (1) |
0.33 (79) |
0.0034 (1) |
0.0015 (5) |
|
HIV‐1GRL98065p40 |
0.032 (5) |
0.38 (12) |
0.28 (8) |
0.34 (10) |
>1 (>38) |
0.19 (6) |
0.011 (3) |
0.21 (70) |
0.18 (600) |
[a] MT‐4 cells were exposed to 100 TCID50 (dose for 50 % infection in cell culture) of each HIV‐1, and inhibition of p24 Gag protein production by each drug was used as an end point. Numbers in parentheses represent n‐fold changes in the EC50 values for each isolate compared to the EC50 values for wild‐type HIV‐1NL4‐3. All assays were conducted in duplicate or triplicate, and data shown are derived from the results of three independent experiments. n.d.=not determined. See reference 113 for details.