TABLE 3.

Characterization of site-directed HIV-1 PR mutants from GS-9770 resistance selections

HIV-1 PR genotypea	GS-9770 concentration (nM) at variant first emergence (Fold EC50)b	Infectivity (% WT)c	EC50 (nM) (fold-change relative to WT)d,e
			GS-9770	ATV	DRV	EFV
Wild type (WT)	N/A	100	3.1 ± 1.6 (1.0)	5.7 ± 3.6 (1.0)	4.4 ± 2.4 (1.0)	1.3 ± 0.7 (1.0)
V82A	N/A	36 ± 5	8.2 ± 3.2 (2.7)	7.6 ± 3.3 (1.3)	3.5 ± 1.5 (0.8)	1.2 ± 0.6 (1.0)
M46L A77I V82A	100 (25)	113 ± 6	8.3 ± 1.8 (2.7)	6.9 ± 1.8 (1.2)	2.5 ± 0.8 (0.6)	1.0 ± 0.2 (0.8)
L24I M46L A77I V82A	100 (25)	122 ± 8	5.9 ± 3.2 (1.9)	4.2 ± 0.8 (0.7)	1.4 ± 0.2 (0.3)	1.1 ± 0.1 (0.9)
L24I M46L I64V A77I V82A	225 (56)	48 ± 4	22.4 ± 7.3 (7.3)	11.7 ± 1.4 (2.1)	2.1 ± 0.5 (0.5)	1.0 ± 0.2 (0.8)

^a Site-directed mutations introduced into HIV-1 protease (PR) sequence of HIV-1_LAI.

^b Resistance selection was initiated as drug concentration equal to 1× the EC₅₀ for GS-9770 (4 nM); N/A = not applicable; the 5× mutant variant (L24I M46L I64V A77I V82A) persisted until end of study (368 total days of selection), reaching 437-fold the EC₅₀.

^c % infectivity values (mean ± standard deviation) obtained from three independent experiments performed in duplicate.

^d EC₅₀ values (mean ± standard deviation) obtained from four independent experiments performed in triplicate. Mean fold-change values (in parentheses) are calculated from the ratio of EC₅₀ of the site-directed mutant virus over the EC₅₀ of WT HIV-1_LAI.

^e ATV = atazanavir; DRV = darunavir; EFV = efavirenz.