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Table 3 Selection of drug resistance to dolutegravir (DTG), bictegravir (BIC), cabotegravir (CAB) and elvitegravir at the final week of passage

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

Virus isolate

Subtype

Acquired mutations at final passage (week 46) of selective drug pressurea

Acquired mutations (week 26–40)b

DTG

BIC

CAB

EVG

RAL

14514

B

R263K

None

None

T66I

–

10387

B

None

None

None

T66I

E92Q

10249

B

R263K

None

None

E92Q

None

14624

B

none

None

H51HY

T66I

T97A, N155H

14637

B

R263K

R263K0

R263K

T66I, E157Q, R263K

N155H

14947

B

R263K

R263K

R263K, S153A

T66I, E138EK, S147G, Q148R

Y143R, L74M, E92V, F121Y, G163GR

5326

B

H51HY

S153Y

L74M, G140S, S147G, Q148K

R263K, S153A

Y143R, L74M, T97A, E157Q

4742

C

None

None

R263K

E92EG, R263KR

T66K

10947

C

R263K

R263K

S147G

E92V, R263K

–

6343

AE

R263K

S153Y

S153Y, G163R

T66I, R263K

–

14515

AG

None

R263K

None

T66I, H51HY

–

96USSN20

AG

R263K

S153FS, E157EK

L74M, E138K, Q148R, R263K

T66I, Q146R, S147G, Q95R

L74M, V79I, E138K, G140A, Q148R

-pNL4.3

B

R263K, M50I

R263K, M50I

S153F

T66I, T97A, S147G, S119R, S153A

T66I, T97A, G163R, D232N

  1. Primary patient-derived viruses were passaged in CBMCs in the presence of escalating concentrations of DTG, BIC, CAB, and EVG for 46 weeks
  2. aGenotypic analysis was performed of at weeks 0, 16, 24 and 46. The mutations acquired at final week of passage are listed in the order of their first appearance. Mutations highlighted in italics conferred high-level resistance. The acquired R263K, H51Y, S153Y/F mutations conferred low-level resistance with 1–10 nM final drug concentrations as compared to the high-level resistance highlighted in italics where the acquisition of complex resistance mutational motifs with CAB or EVG allowed for viral breakthrough at final drug concentrations of 0.1–2.5 µM
  3. bThe emerging resistance patterns to RAL determined in previous studies on viral strains are shown for comparative contextual purposes