Table 3. Amino acid substitutions selected in Gag during passage at a high fixed concentration of GSK3532795 (30xEC50).
Start Virus | MOI | # cultures that gave breakthrough with genotype changes | Daysb | Gag regiona | ||||
---|---|---|---|---|---|---|---|---|
Capsid | Capsid/SP1 | |||||||
219 | 326 | 333 | 362 | 364 | ||||
WTc | 0.05d | 1/2 | 19 | - | - | I333V | - | - |
V370A | 0.005 | 1/3 | 25 | - | - | - | V362I | - |
0.05 | 1/4 | 14 | - | - | - | V362I | - | |
V370A | 0.005 | 2/3 | 31 | H219H/Q | - | I333V/I | - | - |
0.05 | 2/3 | FU | H219Q | - | I333V | - | - | |
ΔT371/ V370A | 0.05d | 1/2 | 17 | - | A326A/T | - | V362V/I | - |
1/2 | FU | H219Q | - | - | - | A364V |
aThere were no changes detected in the matrix or SP2/p6 regions of Gag.
bNumber of days in culture.
cWild type NL4-3. virus
d MOI of 0.005 did not produce virus
EC50, 50% effective concentration; FU, follow up selection using nine sequential passages at two-fold increases in GSK3532795; MOI, multiplicity of infection; SP1, spacer peptide 1, WT, wild-type