Table 1.

Identified Polymorphisms Within the NS5B of the Phenotypes Samples

Patient no.	Therapy	Therapy outcome	Assay outcome (SOF)	Drug sensitivity		Relevant polymorphisms, % (pre→post therapy)
				SOF IC50, μM	RBV IC50, μM	K100R	A150V	A150S	G188D	K206E	T213N	N244I
1	SOF/DAC/RBV	SVR	Sensitive	0.039	0.786	—	V (98)	—	—	—	—	—
2	SOF/VEL	SVR	Sensitive	0.034	0.545	—	—	—	—	—	—	—
3	SOF+OBV /PTV/RBV	SVR	Sensitive	0.011	0.419	—	—	—	—	—	—	—
4	SOF/DAC	SVR	Sensitive	0.054	0.19	—	—	—	—	E (98)	—	—
5	SOF/LDV/RBV	Relapse	Sensitive	0.06	0.43	—	—	—	—	E (99)	—	—
6	SOF/DAC/RBV	Relapse	Sensitive	0.033	0.886	—	—	—	—	E (99)	—	—
7	SOF/LDV/RBV	Relapse	Sensitive	0.04	0.72	—	V (98)	—	—	—	—	—
8	SOF/LDV	Relapse	Sensitive	0.02	0.701	—	—	—	—	—	—	—
9	SOF/DAC/RBV	Relapse	Insensitive	>0.25	>1.25	R (65→98)	—	S (98–99)	D (98→97)	—	N (98→99)	I (94–99)
10	SOF/LDV/RBV	Relapse	Insensitive	>0.25	>1.25	R (97→98)	V (54–98)	—	—	E (89→99)	—	—
11	SOF/LDV/RBV	Relapse	Insensitive	>0.25	>1.25	—	V (98–95)	—	—	E (98→99)	—	—
12	SOF/DAC/RBV	Relapse	Insensitive	>0.25	>1.25	—	V (98–97)	—	—	E (100→99)	—	—
13	SOF/LDV/RBV	Relapse	Insensitive	>0.25	>1.25	—	V (98–99)	—	—	E (98→99)	—	—
14	SOF/LDV/RBV	Relapse	Insensitive	>0.25	>1.25	—	V (99)a	—	—	E (100)a	—	—

NOTE. Patients were divided into 3 groups (SVR-sensitive, relapse-sensitive, and relapse-insensitive) based on therapy and assay outcomes. Samples were deemed to be SOF-insensitive if a single dose of the antiviral drug (0.25 μM) did not reduce the HCV RNA levels to <80% of the no-drug control in the capture fusion assay. Polymorphisms were identified by comparison of NS5b next-generation sequencing data from drug-sensitive vs drug-insensitive samples. The majority of the polymorphisms were identified in the assay-insensitive group, with a specific pattern (A150V and K206E) seen in patients 10–14. Percentage values indicate the frequency of each polymorphism present in the viral populations.

LDV, ledipasvir.

^aNo post-treatment sequencing data were obtained for sample 14 due to low viral load post relapse.