NS5b GT5 | SHARED - A Hepatitis C Resource

Sofosbuvir

	1. Harvoni US Product Lable
	2. Xu et al. (2017) Antiviral therapy 22:587-97.



	Sofosbuvir in GT5
	EC50 (uM)	Fold-shift	Phenotype	Replicative Fitness (2)	Reference	Clinical RAS	Comments
WT	0.014-0.11	1x	likely susceptible
M289L		2.3x	likely susceptible	121	2
S282T		19x	resistance likely	3.2	1,2	Yes	clinical RAV n=1
S282T+M289L		11x	resistance likely	6	2		selected in replicon
S282R			resistance likely				catalytic triad
S282G			resistance likely				catalytic triad
M289I			resistance possible		1		clinical TE RAV n=1



		The current dataset does not contain resistance possible classification
		>2.5x FS, resistance likely
		All S282 substitutions are considered resistance likely

		Multiple RASs:
		Data for variants with multiple mutations take precedence over estimation from individual RASs
		If RAV data are not available, follow rules for individual RASs in the variant
		2 likely susceptible = likely susceptible
		2 resistance possible = resistance likely
		likely susceptible + resistance possible = resistance possible
		>/= 1 resistance likely RASs = resistance likely


		Clinical RAV:
		without data but observed in Clinical VF = resistance possible
		likely susceptible RASs + clinical RAV = resistance possible


		Positions monitored for "Mutations Detected, effects unknown"
		159, 282, 316, 320, 321

		For NGS data: only RASs with >/=2% frequency will be included

		strikthrough= mutations obsreved in VFs with NGS but deemed unimportant by FDA.

1. Harvoni US Product Lable

2. Xu et al. (2017) Antiviral therapy 22:587-97.