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

Table 4 Cell culture selections of viral recombinant strains bearing the integrase from patient samples with and without the E157Q polymorphisms

Virus^a	Codon 157	Acquired mutations at final passage (week 36–38) of selective drug pressure^b
Virus^a	Codon 157	DTG	BIC	CAB	EVG	RAL
pNLWT	WT	R263K, M50I	R263K, M50I	S153F	T66I, T97A, S147G, S119R, S153A	ND
pNL157Q	E157Q	R263K, M50IM	Q146R	R263K, M50I	T66I, S147G, Q95K	E92Q
E78001	WT	S153F	S153Y	R263K, M50I	T66I, Q146R, S230R	Y143R, L74M, V151I
E78003	WT	S147G, H51Y	R263K, M50I	N155H	Q95R, S147G, Q148R	T97A, G163R, V151I, L74M
E78004	WT	Q146R, Q95KQ	Q146R, Q95KQ	Q148R, E138K, G140GS, L74I	T66I, Q95K, E157Q, S230R	T66A, A128T, Y143G, G163R, V151I
E78005	WT	R263K	S153Y	S153F	T66A, Q146I	T97A, Y143R, V151I
E78060	WT	R263K	R263K, M50I	Q146L	T97A Q146R, T66IT	T97A, E157Q, A128AT, V151I
E78110	E157Q	R263K, M50I	R263K	R263K	T66I, R263K, M50I	Y143R
E102430	E157Q	R263K	R263K	R263K, M50I	E138K, Q148K	V151S, L74LM
E102952	E157Q	S153F	R263K, M50I	R263K	T66I, E92Q	Q148R, E138K, G140A, V151IV
E103211	E157Q	R263K	R263K	R263K, H51N	S147G, Q148R, E138K	Y143R
E103212	E157Q	R263K	R263K	R263K, M50I	H51Y, S147G, T97A	T97A

The underline refers to the de novo aquisition of E157Q during selection
^aIntegrase derived from clinical isolates with or without the E157Q substitution were inserted into integrase-depleted pNL4.3 plasmids. Isolated recombinant viruses were serially passaged in escalating concentrations of dolutegravir (DTG), bictegravir (BIC), cabotegravir (CAB), elvitegravir (EVG) or raltegravir (RAL) over the course of 36 weeks
^bGenotypic analysis was performed of at weeks 0, 16, 24 and 36–38. 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

ISSN: 1742-4690