Skip to main content

Table 6 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)

From: Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir

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 ×)

  1. The underline refers to the de novo aquisition of E157Q during selection
  2. aViruses were harvested at the designated week of selection, amplified in PHA-stimulated CBMCs and genotyped. Viruses were co-cultured in PHA-stimulated CBMCs to deduce drug susceptibility against dolutegravir (DTG), bictegravir (BIC), cabotegravir (CAB), elvitegravir (EVG) and raltegravir (RAL). Samples in italics represent greater than 5-fold reduction in drug susceptibility. pNL4.3 recombinant virus are included as controls with R263K and S153Y mutations inserted by site-directed mutagenesis