Table 4.

Patients with virologic failure: polymorphisms/substitutions in NS3 and NS5A at baseline and time of failure

	Treatment historya	Treatment duration (weeks)	HCV subtype	Cirrhosis Y/N	Reason for nonresponse	NS3 variants		NS5A variants
						Baseline	At failure	Baseline	At failure
SURVEYOR‐2
1b	Experienced	12	3a	N	Relapse	None	Y56H + Q168R	A30K	A30K + Y93H
2	Experienced	12	3a	N	Breakthrough	A166S	Y56H + A166S + Q168L	A30K	A30K + Y93H
3	Experienced	12	3a	N	Relapse	None	None	Y93H	L31F + Y93H
4	Experienced	16	3a	Y	Relapse	A166S	None	None	M28G
5	Experienced	12	3a	N	Relapse	None	None	A30K	A30K + Y93H
6	Experienced	12	3a	N	Relapse	None	None	Y93H	Y93H
7	Experienced	16	3a	N	Relapse	None	Y56H + Q168R	A30K	A30K + Y93H
8	Experienceda	16	3a	Y	Relapse	None	None	None	L31F + Y93H
9b	Experienced	16	3a	Y	Breakthrough	A166S	A156G + A166S	None	A30K + Y93H
ENDURANCE‐3
10	Naïve	12	3a	N	Breakthrough	Q168R	Y56H + Q168R	A30V/K, Y93H	A30K + Y93H
11	Naïve	12	3a	N	Relapse	None	None	None	A30G, Y93H
12b	Naïve	12	3a	N	Relapse	None	Reinfectionc	None	Reinfectionb
13	Naïve	12	3b	N	Relapse	None	Q80K	V31M	V31M + Y93H
14	Naïve	8	3a	N	Relapse	T54S	T54S	None	None
15	Naïve	8	3a	N	Relapse	None	Q168L	A30K	A30K + Y93H
16	Naïve	8	3a	N	Relapse	A166S	Y56H, Q168L	A30K	A30K + Y93H
17b	Naïve	8	3a	N	Failed to Suppress	A166S, Q168R	Q80R, A156G	A30K	A30K + Y93H
18	Naïve	8	3a	N	Relapse	A166S	A166S	None	Y93H
19	Naïve	8	3a	N	Relapse	None	Y56H	A30K	A30K + Y93H
MAGELLAN‐2
20	Naïve	12	3a	N	Relapse	None	Y56H	Y93H	Y93H
EXPEDITION‐2
21b	Naïve	12	3a	Y	Breakthrough	None	Y56H	A30V	S24F + M28K

Detection of baseline polymorphisms and treatment‐emergent substitutions was done with next‐generation sequencing using a 15% detection threshold relative to subtype‐specific reference sequence. For samples with multiple variants (polymorphisms/substitutions) within a target, if individual variants were detected at ≥90% prevalence, they are considered to be linked and denoted by “+”, whereas if one or more of the variants was detected at <90% prevalence, the variants are separated by a comma. Amino acid positions included in the analysis: 36, 43, 54, 55, 56, 80, 155, 156, 166 and 168 in NS3; 24, 28, 29, 30, 31, 32, 58, 92 and 93 in NS5A.

^aAll patients listed with treatment experience were experienced with pegIFN/RBV, except for patient #8, who was experienced with SOF/RBV.

^bNonadherent to DAA and excluded from mITT analysis (as virologic failure unrelated to efficacy); additional details in Table S2.

^cPatient was infected with a GT3a virus at the time of virologic failure with viral sequences that were distinct from the sequences present at baseline and was determined to have been HCV reinfected.