TABLE 3.
Genotype of HIV-1 variants selected in vitro in the presence of tBPQAs
| Selected virusa | Duration of selection | Compound concentration reached | Integrase mutations identifiedb | Integrase mutationsc |
|---|---|---|---|---|
| day | nm | |||
| HIV-1 IIIbd | Y99H (0%), V126I (0%), A128T (0%), G134E (0%), H171Q (0%), T174I (0%), V201I (0%), N222K (0%) | |||
| GS-A P2 | 17 | 160 | A128T, G134E | A128T (83.3%), G134E (12.5%) |
| GS-A P5 | 42 | 1,280 | A128T, G134E, H171Q, V201I | A128T/H171Q/V201I (33.3%), G134E/H171Q/V201I (62.5%), G134E/H171Q (4.2%) |
| GS-A P6 | 50 | 2,560 | A128T, G134E, H171Q, T174I, V201I | A128T/H171Q/V201I (20.8%), A128T/H171Q (4.2%), A128T/T174I (70.8%), G134E/H171Q/V201I (4.2%), G134E/H171Q (4.2%) |
| GS-A P8d | 69 | 10,240 | A128T, T174I | A128T/T174I (100%) |
| GS-B P3 | 37 | 60 | Y99H, N222K | Y99H/N222K (100%) |
| GS-B P5 | 49 | 240 | Y99H, V126I, T174I, N222K | Y99H/N222K (83.3%), Y99H/T174I/N222K (4.2%), V126I/T174I (8.3%), V126I/T174I/N222K (4.2%), |
| GS-B P6d | 59 | 480 | Y99H, V126I, T174I, N222K | Y99H/N222K (4.2%), V126I/T174I (33.3%), V126I/N222K (4.2%), V126I/T174I/N222K (50%) |
a Twenty-four clones from each viral passage were sequenced using two sequencing primers.
b A128T was not selected with GS-B, but three new mutations were selected: Y99H, V126I, and N222K.
c Percentage of total clones analyzed is shown in parentheses.
d HIV-1 IIIb contains 42% T124/T125 and 58% A124/T125. By passage 8 of selection with GS-A, 100% of the clones are T124/T125. By passage 6 of selection with GS-B, 100% of the clones are A124/T125.