Viral variant-drug selection week (drug)a | Acquired resistance mutations | EC50 (nM) in CBMCs (fold-resistance relative to WT control) | ||||
---|---|---|---|---|---|---|
DTG | BIC | CAB | EVG | RAL | ||
pNL4.3 | WT | 0.71 | 0.49 | 0.39 | 0.13 | – |
pNL4.3-R263K | R263K | 1.56 (2.2 ×) | 1.60 (3.3 ×) | 0.91 (2.4 ×) | 0.79 (6.1 ×) | – |
pNL4.3-S153Y | S153Y | 3.34 (4.7 ×) | 3.40 (7.0 ×) | 1.01 (2.6 ×) | <0.3 (2 ×) | – |
pNL4.3-S153F | S153F | 0.45 (0.63 ×) | 0.63 (1.3 ×) | 0.56 (1.4 ×) | <0.3 | – |
E78004 No drug | WT | 0.49 | 1.26 | 0.27 | 0.65 | 1.18 |
E78004 Wk18 CAB (0.0025 μM) | Q95KQ, Q148R | 1.28 (2.6 ×) | 1.17 (0.9 ×) | 0.67 (2.5 ×) | 0.90 (32 ×) | 1.64 (1.4 ×) |
E78004 Wk26 CAB (0.005 μM) | Q95KQ, Q148R, E138EK | 1.60 (3.3 ×) | 1.77 (1.4 ×) | 3.04 (11.3 ×) | 93.57 (144 ×) | 20.76 (18 ×) |
E78004 Wk36 CAB (0.25 μM) | Q148R, E138K, L74I, G140GS | 12.34 (25 ×) | 6.08 (5.3 ×) | 23.6 (87 ×) | 36.16 (57 ×) | 3182 (> 100 ×) |
E78004 No drug | WT | 0.66 | 0.66 | 0.43 | 0.79 | 1.69 |
E78004 Wk18 EVG (0.25 μM) | T66I, Q95K, E157EQ | 0.59 (0.9 ×) | 0.56 (0.9 ×) | 0.24 (0.5 ×) | 29.10 (37 ×) | 14.57 (8.6 ×) |
E78004 Wk26 EVG (0.25 μM) | T66I, Q95K, E157Q | 0.53 (0.8 ×) | 0.38 (0.6 ×) | 0.39 (0.9 ×) | 69.76 (89 ×) | 7.98 (4.7 ×) |
E78004 Wk36 EVG (2.5 μM) | T66I, Q95K, E157Q, S230R | 0.06 (0.1 ×) | 0.01 (0.01 ×) | 0.03 (0.1 ×) | 123.10 (156 ×) | 5.47 (3.2 ×) |
E78060 No drug | WT | 0.52 | 0.92 | 0.45 | 0.46 | 2.43 |
E78060 Wk36 RAL (0.5 μM) | T97A, A128AT, E157Q, V151I | 0.31 (0.6 ×) | 0.30 (0.3 ×) | 0.22 (0.5 ×) | 23.79 (52 ×) | 49.83 (21 ×) |
E102952 No drug | WT (E157 Q) | 0.09 | 0.25 | 0.13 | 0.33 | 0.44 |
E102952 Wk18 RAL (0.025 μM) | Q148R (E157Q) | 0.17 (1.8 ×) | 0.10 (0.4 ×) | 0.14 (1 ×) | 0.41 (1.3 ×) | 0.75 (1.7 ×) |
E102952 Wk38 RAL (20 μM) | Q148R, E138K, G140A, V151IV (E157Q) | 5.46 (58 ×) | 2.63 (10.6 ×) | 2.13 (16.3 ×) | 1255 (> 100 ×) | 1519 (> 100 ×) |