Hepatitis C virus in the new era: Perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy

Table 1 Boceprevir and telaprevir response guided therapy and futility rules

End-point	Boceprevir	Telaprevir
RGT	Non-cirrhotic treatment naïve patients, previously relapsers or partial responders	Non-cirrhotic treatment naïve patients previously relapsers
	HCV-RNA undetectable at weeks 8 and 24	HCV-RNA undetectable at weeks 4 and 24
Futility rules	HCV-RNA > 100 IU/mL at week 12	HCV-RNA > 1000 IU/mL at weeks 4 and 12
	HCV-RNA detectable at week 24	HCV-RNA detectable at week 24

HCV: Hepatitis C virus.

Table 2 Qualitative and quantitative hepatitis C virus RNA assays available for clinical use

Assay	Manufacturer	Method	LOD, IU/mL(dynamic range, IU/mL)
Qualitative
Amplicor HCV v2.0	Roche molecular system	RT-PCR (manual)	50
Cobas Amplicor HCV v2.0	Roche molecular system	Semi-automated RT-PCR	50
Ampliscreen1	Roche molecular system	Semi-automated RT-PCR	< 50
Versant HCV RNA	Siemens healthcare diagnostics	Semi-automated TMA	10
Procleix HIV-1/HCV1	Chiron corporation	TMA (manual)	< 50
Quantitative
Amplicor HCV Monitor	Roche molecular system	RT-PCR (manual)	N/A (600-700000)
Cobas Amplicor HCV Monitor v2.0	Roche molecular system	Semi-automated RT-PCR	600 (600-500000)
Versant HCV 1.0 Assay K-PCR	Siemens healthcare diagnostics	Semi-automated RT-PCR	15 (15-100000000)
Abbott RealTime HCV Assay	Abbott diagnostics	Semi-automated RT-PCR	12 (12-100000000)
LCx HCV RNA Quantitative Assay	Abbott diagnostics	Semi-automated RT-PCR	25 (25-2630000)
Cobas Ampliprep/Taqman	Roche molecular system	Semi-automated RT-PCR	15 (15-100000000)

¹Used for blood screening only. HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; RT-PCR: Reverse transcription-polymerase chain reaction; LOD: Limit of detection.

Table 3 Degree of telaprevir and boceprevir resistance associated mutations

Degree of resistance	Mutations	Fold increase
Low level	V36A/M/C	3.5-7
	T54A/S	6-12
	R155K/T/Q	8.5-11
Intermediate	V36A/M + R155K/T	57-71
High level	A156V/T	74-410
	V36A/M + A156V/T	> 700

Table 4 Resistance associated mutations and cross-resistance to approved and advanced phase-studied NS3/4 protease inhibitors

Drug	Molecule	V36A/M	F43S	T54S/A	V55A/K	Q80R/K	S122A/G/R	I132V	R155K/T/Q	A156S/D/T/V	V158I	D168A/V/T/H	I170F/T1V170A/T1	M175L
Telaprevir	Linear	-2		-2				-3	-2	-2		-3
Boceprevir	Linear	-2		-2	-2				-2	-2	-3		-3	-3
Faldaprevir	Linear								-2	-3		-2	-3
Danoprevir	Macrocyclic					-3			-2			-2	-3
Vaniprevir	Macrocyclic		-3						-2	-3		-2
Simeprevir	Macrocyclic					-2	-3		-2	-3		-2

¹The I170F/T and the V170A/T mutations were detected in hepatitis C virus genotype 1a and 1b, respectively, in which I and V represent the consensus amino acid, respectively;

²Indicates resistance associated mutations detected in virologically failed patients and confirmed by phenotypic tests;

³Indicates mutations detected as additional mutations or still of uncertain significance.