Table 5 Phenotypic drug susceptibility of viral strains to integrase strand transfer inhibitors (INSTIs) harvested at the designated week of selection with cabotegravir (CAB) or elvitegravir (EVG)
Virus selection week druga | Acquired resistance mutations | EC50 (nM) in CBMCs (fold-resistance relative to WT control) | ||||
|---|---|---|---|---|---|---|
DTG | BIC | CAB | EVG | RAL | ||
6343 No drug | WT | 0.10 | 0.17 | 0.23 | 0.21 | ND |
6343 Wk 46 CAB | S153Y, G163R | 0.60 (6 ×) | 1.33 (8 ×) | 0.87 (3.2 ×) | 0.53 (2.5 ×) | ND |
5326 No drug | WT | 0.77 | 0.41 | 0.20 | 0.253 | 1.12 |
5326 Wk 45 EVG (1 µM) | S263K, S153A | 0.52 (0.7 ×) | 0.53 (1.3 ×) | 0.19 (1.0 ×) | 53 (212 ×) | 1.12 (1.0 ×) |
5326 Wk 17 CAB (0.01 µM) | Q148K | 1.57 (2.0 ×) | 0.90 (2.2 ×) | 0.61 (3.1 ×) | 2.96 (11.8 ×) | 3.57 (3.2 ×) |
5326 Wk 28 CAB (0.5 µM) | Q148K, G140S, G147GS | 3.60 (4.7 ×) | 0.72 (1.8 ×) | 8.07 (40 ×) | 180 (720 ×) | 66.5 (60 ×) |
5326 Wk 48 CAB (1.0 µM) | Q148K, G140S, S147G, L74M | 125 (162 ×) | 49.01 (120 ×) | 139.7 (700 ×) | 3429 (> 1000 ×) | 1007 (900 ×) |
96USSN20 No drug | WT | 0.58 | 0.77 | 0.29 | 0.20 | 1.60 |
96USSN20 Wk27 EVG (2.5 µM) | T66I, T97A, Q147G | 0.40 (0.7 ×) | 0.80 (1 ×) | 1.20 (4 ×) | >100 (> 500 ×) | 1.7 (1 ×) |
96USSN20 Wk 17 CAB (0.025 µM) | Q148R, E138EK, R263KR | 8.08 (14 ×) | 5.83 (8 ×) | 2.40 (8.3 ×) | 22.35 (112 ×) | 12.01 (7 ×) |
96USSN20 Wk 27 CAB (0.25 µM) | Q148R, E138K, R263K, L74LM | 10.0 (17 ×) | 9.01 (12 ×) | >30 (> 100 ×) | >300 (> 1500 ×) | 300 (188 ×) |
96USSN20 Wk 45 CAB (0.5 µM) | Q148R, E138K, R263K, L74M | 13.93 (24 ×) | 13.40 (17 ×) | 47.8 (165 ×) | 1612 (8060 ×) | 568 (355 ×) |