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

Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Anstett, Kaitlin; Mésplède, Thibault; Routy, Jean-Pierre; Robbins, Marjorie A.; Brenner, Bluma G.

doi:10.1186/s12977-018-0440-3

Table 7 Viral outgrowth of elvitegravir (EVG) resistant viruses switched to dolutegravir (DTG), bictegravir (BIC) or cabotegravir (CAB)

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

Virus	Initial EVG selection	Drug switch selection		Resistance mutations at week 27	Lost EVG mutations	Acquired mutations
Virus	Initial EVG selection	2nd drug	Drug (µM)	Resistance mutations at week 27	Lost EVG mutations	Acquired mutations
6343	EVG Wk 46	Pre-switch	0.25	T66I, R263K
6343		DTG	0.010	M50MI, R263K	T66I	M50IM
6343		BIC	0.050	R263K	T66I
6343		CAB	0.050	R263K	T66I
6343		No drug		R263K	T66I
14637	EVG Wk 46	Pre-switch	1.0	T66I, E157Q, R263K
14637		DTG	0.010	E157Q, R263K	T66I
14637		BIC	0.025	E157Q, R263K	T66I
14637		CAB	0.050	E157Q, R263K	T66I
14637		No drug		E157Q, R263K	T66I
5326	EVG Wk 46	Pre-switch	1	S153A, R263K
5326		DTG	0.010	S153A, R263K
5326		BIC	0.010	S153A, R263K
5326		CAB	0.050	S153A, R263K
5326		No drug		S153A	R263K
14624	EVG Wk 46	Pre-switch	1	T66I
14624		DTG	0.005	T66I, L74M, E138K, S147G, M154IM		L74M, E138K, S147G, M154IM
14624		BIC	0.010	H51HY	T66I	H51HY
14624		CAB	0.10	T66I, L74M, G140GS, S147GS		L74M, G140GS, S147GS
14624		No drug		T66I
14947	EVG Wk 46	Pre-switch	5	T66I, E138EK, S147G, Q148R
14947		DTG	0.005	T66I, E138EK, S147G, Q148R, S230N		S230N
14947		BIC	0.025	T66I, E138EK, S147G, Q148R, S230N		S230N
14947		CAB	0.100	T66I, L74M, E138EK, S147G, Q148R, S230N		L74M, S230N
14947		No drug		T66I, S147G, S230NS	E138EK, Q148R	S230NS
96USSN20	EVG Wk 46	Pre-switch	2.5	T66I, Q146R, S147G
96USSN20		DTG	0.100	T66I, Q146R, S147G, E138E1AEKT, Q148R	Q146R	E138AEKT, Q148R
96USSN20		BIC	0.050	T66I, Q146R, S147G, E138A, T97A	Q146R	T97A, E138A, Q148R
96USSN20		CAB	0.25	T66I, Q146QR, S147G, E138A, Q148QR	Q146QR	E138A, Q148QR
96USSN20		No drug		T66I, S147G	Q146R
pNL4.3	EVG Wk 46	Pre-switch	2.5	T66I, T97A, S147G, V151I, S153A
pNL4.3		DTG	0.025	T66I, T97A, S147G, V151I, S153A
pNL4.3		BIC	0.025	T66I, T97A, S147G, V151I, S153A
pNL4.3		CAB	0.250	T66I, T97A, S147G, V151I, S153A
pNL4.3		No drug		T66I, T97A, S147G, V151I, S153A

Patient-derived viral strains, subjected to EVG selective pressure for 46 weeks, were switched to serially increasing concentrations of DTG, BIC, CAB or no drug for 27 weeks. Genotyping was performed at week 27 and re-genotyped to monitor the loss and acquisition of mutations

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ISSN: 1742-4690

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