Sofosbuvir and ABT-450: Terminator of hepatitis C virus?

Table 1 Representative direct acting antiviral agent from 2011 to January, 2013

DAA	HCV genotype	Course of DAA (wk)	Course of therapy (wk)	Dose	With or without pegIFN-α	Published year	Ref.
Telaprevir	1a/1b/1c/unknown	12/8	20/24/44/48	750 mg (tid)	With	2011	[30-32]
Boceprevir	1a/1b/unknown	24/32/44	28/36/48	800 mg (tid)	With	2011	[33-34]
Daclatasvir	1a/1b	24	24	60 mg (qd)	With or without	2012	[36]
Asunaprevir	1a/1b	24	24	600 mg (bid)	With or without	2012	[36]
Sofosbuvir	1/2/3	8/12	8/12	400 mg (qd)	Without	2013	[37]
ABT-450	1a/1b	12	12	250/150 mg (qd)	Without	2013	[38]

qd: Once daily; bid: Twice daily; tid: Thrice daily; DAA: Direct acting antiviral agent; HCV: Hepatitis C virus; pegIFN-α: Peginterferon-α.

Table 2 Overview of 95 hepatitis C patients under sofosbuvir regimen

Group	n	Genotype (n)	Status before treatment	Therapeutic schedule	SVR rate
1	10	2/3 (4/6)	Untreated	Sofosbuvir + RBV 12 wk	100%
2	9	2/3 (3/6)	Untreated	(Sofosbuvir + RBV 12 wk) + pegIFNα-2a 4 wk	100%
3	10	2/3 (4/6)	Untreated	(Sofosbuvir + RBV 12 wk) + pegIFNα-2a 8 wk	100%
4	11	2/3 (4/7)	Untreated	Sofosbuvir + RBV + pegIFNα-2a 12 wk	100%
5	10	2/3 (3/7)	Untreated	Sofosbuvir 12 wk	60%
6	10	2/3 (0/10)	Untreated	Sofosbuvir + RBV + pegIFNα-2a 8 wk	100%
7	10	1a/1b (9/1)	No response to prior therapy	Sofosbuvir + RBV 12 wk	10%
8	25	1a/1b (22/3)	Untreated	Sofosbuvir + RBV 12 wk	84%

The dose of sofosbuvir is 400 mg (qd), peginterferon-α (pegIFN-α)-2a is 180 μg (qw), ribavirin (RBV) is 500 mg (bid) for patients with body weight < 75 kg, and RBV is 600 mg (bid) for patients with body weight > 75 kg. qd: Once daily; bid: Twice daily; qw: Once weekly; SVR: Sustained virologic response.

Table 3 Overview of 50 hepatitis C patients under ABT-450 regimen

Group	n	Genotype (n)	Status before treatment	Therapeutic schedule	Usage	SVR rate2
1	19	1a/1b (17/2)	Untreated	ABT-450 + ritonavir + ABT-333 + RBV 12 wk	ABT-450, 250 mg (qd)	95%
					Ritonavir, 100 mg (qd)
					ABT-333, 400 mg (bid)
					RBV, 1000 or 1200 mg/d1
2	14	1a/1b (11/3)	Untreated	ABT-450 + ritonavir + ABT-333 + RBV 12 wk	ABT-450, 150 mg (qd)	93%
					Ritonavir + ABT-333 + RBV Ditto
3	17	1a/1b (16/1)	No or partial response to prior therapy	ABT-450 + ritonavir + ABT-333 + RBV 12 wk	ABT-450, 150 mg (qd)	47%
					Ritonavir + ABT-333 + RBV Ditto

¹Body weight < 75 kg, 1000 mg/d, divided into doses of 400 and 600 mg, bid; Body weight ≥ 75 kg, 1200 mg/d, 600 mg, bid;

²Sustained virologic response (SVR) in this study was defined as an

Table 4 Major adverse events during sofosbuvir and ABT-450 regimens

Adverse events	Sofosbuvir regimen	ABT-450 regimen1
Headache	32%-90%	14%-26%
Fatigue	10%-70%	35%-47%
Insomnia	10%-67%	0%-26%
Nausea	0%-44%	21%-24%
Rash	10%-60%	6%-21%
Anemia	0%-44%	No data
Dizziness	4%-44%	5%-29%
Myalgia	0%-40%	No data
Diarrhea	0%-30%	No data
Vomiting	No data	0%-21%
Irritability	0%-36%	No data
Pruritus	0%-33%	0%-21%
Decreased appetite	0%-50%	No data
Upper respiratory tract infection	0%-20%	No data
Arthralgia	0%-30%	No data
Back pain	0%-22%	No data
Pyrexia	0%-18%	No data

¹Adverse events during ABT-450 regimen were only listed those that occurred in more than 20% of patients.

Table 5 Interleukin-28B polymorphism in sofosbuvir and ABT-450 era

Group	Status before treatment	IL-28B CC (n)	IL-28B CT (n)	IL-28B TT (n)	SVR rate
Sofosbuvir
1	Untreated	5	4	1	100%
2	Untreated	4	4	1	100%
3	Untreated	4	4	2	100%
4	Untreated	4	5	2	100%
5	Untreated	2	6	2	60%
6	Untreated	3	6	1	100%
7	No response to prior therapy	2	5	3	10%
8	Untreated	11	12	2	84%
ABT-450
1	Untreated	10/9	7/7	2/2	95%
2	Untreated	5/4	7/7	2/2	93%
3	No or partial response to prior therapy	0/0	12/6	5/2	47%

IL-28B: Interleukin-28B; SVR: Sustained virologic response.

Table 6 Outcome of representative direct acting antiviral agent-based therapy for genotype 1 null responders

Authors	n	Therapeutic schedule	SVR rate
Zeuzem et al[32]	37	(pegIFN-α2a + RBV) 4 wk + (pegIFN-α2a + RBV + telaprevir) 12 wk + (pegIFN-α2a + RBV) 32 wk	33%
Bacon et al[33]	58	(pegIFN-α2b + RBV) 4 wk + (pegIFN-α2b + RBV + boceprevir) 44 wk	52%
Lok et al[36]	11	Daclatasvir + asunaprevir 24 wk	36%
Lok et al[36]	10	Daclatasvir + asunaprevir + pegIFN-α2a + RBV 24 wk	90%
Gane et al[37]	10	Sofosbuvir + RBV 12 wk	10%
Poordad et al[38]	7	ABT-450 + ritonavir + ABT-333 + RBV 12wk	43%

pegIFN-α: Peginterferon-α; SVR: Sustained virologic response; RBV: Ribavirin.