Viral dynamics among HCV infected patients with different genotypes treated with genotypic specific or pan-genotypic direct-acting antiviral agent combinations

Figures & data

Table 1 Patient characteristics

	Treatment		p-value*
	Genotypic specific Regimens (GSR) N° 169	Pan-genotypic Regimens (PGR) N° 186
Gender			0.88
Male	85 (50.3%)	96 (51.6%)
Female	84 (49.7%)	90 (48.4%)
Nationality			0.74
Italian	164 (97.1%)	182 (97.8%)
Other	5 (2.9%)	4 (2.2%)
Genotype
1a	20 (11.8%)	35 (18.8%)
1b	85 (50.3%)	44 (23.6%)
2	28 (16.5%)	76 (40.9%)
3	12 (7.1%)	25 (13.5%)
4	24 (14.3%)	6 (3.2%)
HIV-1/HBVcoinfection	28 (16.6%)	40 (21.5%)	0.28
BL PLT, per cubic ml (range)	188,000 (26,000–940,000)	196,000 (64,000–870,000)	0.17
BL ALT, U/liter	51.4±49.7	64.3±93.1	0.22
BL AST, U/liter	41.8±33.8	53.8±85.1	0.54
BL Bilirubin, µmol/liter	14.0±7.8	41.0±330.0	0.67
Serious adverse event (grade 3–4, WHO)	11 (6.5%)	8 (4.3%)	0.48
Baseline median HCV viral load (UI/ml log10)	5.71 (range 3.1–7.1)	5.74 (range 3.0–6.9)	0.39
Naïve	139 (82.2%)	146 (78.5%)	0.42
IFN/RBV experienced	30 (17.8%)	40 (21.5%)	0.42
DAA experienced	1 (0.6%)	1 (0.5%)	1.00
Cirrhosis (>12.5 Kpa) HCV RNA>6.000.000 IU/ml Baseline drug RASs Previous IFN-treatment	29 (17.1%) 10 (5.9%) 9/140 (6.4%) 30 (17.7%)	20 (10.75%) 17 (9.1%) 17/176 (9.7%) 40 (21.5%)	0.09 0.32 0.41 0.42

Note: *Fisher’s exact or Chi-square test.

Abbreviations: BL, baseline; PLT, platelet; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Figure 1 End of therapy SVR rates according to different treatments.

Figure 2 Kaplan–Meier curves of cumulative undetectable HCV RNA levels in patients according to GSR vs PGR (A) or in patients grouped as having GSR (B) or PGR (C). p-values were obtained using the log-rank test.

Figure 3 Kaplan–Meier curves of cumulative HCV RNA undetectable levels according to genotype and patients grouped as having GSR (A), PGR (B). Kaplan–Meier curves of cumulative HCV RNA undetectable levels according to genotype (C-G). p-values were obtained using the log-rank test.

Table 2 DAA baseline RASs in HCV genes

Group of tretament	# patient			Baseline RASs
		Genotype	Therapy	NS3	NS5A	NS5B	Outcome
GSR	1	1a	Omb,Par,Das,RTV, RBV	None	31M	None	Responder
	2	1b	Omb,Par,Das,RTV, RBV	None	93H	None	Responder
	3	1b	Omb,Par,Das,RTV, RBV	None	28M,93H	None	Relapser
	4	1b	Led, Sof	None	93H	None	Responder
	5	1b	Elb+Graz	None	93H	None	Responder
	6	1b	Elb+Graz	56F	None	None	Responder
	7	1b	Elb+Graz	None	93H	None	Relapser
	8	1b	Elb+Graz	None	93H	None	Responder
	9	1b	Elb+Graz	None	93H	None	Responder
PGR	10	1a	Sof +Vel	None	31M	None	Responder
	11	1a	Sof +Vel	None	30R	None	Responder
	12	1a	Pib+Gle	None	28T+30R	None	Responder
	13	1b	Sof +Vel	None	None	556G	Responder
	14	1b	Sof +Vel	None	None	448H, 451Y	Responder
	15	1b	Sof +Vel	None	None	451H, 556G	Responder
	16	1b	Sof +Vel	None	93H	159F	Responder
	17	1b	Sof +Vel	None	None	159F	Responder
	18	1b	Sof +Vel	None	28M+93H	None	Responder
	19	1b	Sof +Vel	None	None	159F	Responder
	20	1b	Sof +Vel	None	None	159F	Responder
	21	1b	Sof +Vel	None	None	159F	Responder
	22	1b	Pib+Gle	None	93H	None	Responder
	23	2c	Sof +Vel	None	31M	None	Relapser
	24	3a	Sof +Vel	None	93H	None	Responder
	25	3a	Sof +Vel	None	93H	None	Responder
	26	3a	Sof +Vel	None	30K	None	Responder

Notes: RASs to ongoing therapy and drug regimen-including combination with reduced sensitivity are in Bold; the RASs not correlated with the ongoing therapy are in plain style.

Abbreviations: Omb, ombitasvir; Par, paritepravir; Das, dasabuvir; RTV, ritonavir; RBV, ribavirin; Led, ledipasvir; Sof, sofosbuvir; Elb, elbasvir; Graz, grazoprevir; Vel, velpatasvir; Pib, pibrentasvir; Gle, glecaprevir.

Table 3 DAA RASs in patients with virologic failure

Patient	Genotype	Therapy (weeks)	RASs								Outcome	Risk factor	HCV RNA at 4 weeks
			NS3		NS5A			NS5B
			Baseline	At Failure	Baseline		At Failure	Baseline		At Failure
1	1b	Omb,Par, Das,RTV (12)	None	None	28M,93H		28M,93H	None		None	Relapser	IFN*	<12 IU/ml
2	2	Dac,Sof (12)	None	None	None		None	None		None	Relapser	Cirrhosis	NEG
3	1b	Elb,Graz (12)	174F	174F	None		93H	nd		None	Relapser	IFN	26 IU/ml
4	1b	Elb,Graz (12)	None	56F	None		31I	None		None	Relapser	None	<12 IU/ml
5	1b	Elb,Graz (12)	None	56H,168V	93H		31V, 93H	None		None	Relapser	Cirrhosis, IFN	20 IU/ml
6	1a	Sof,Vel (12)	None	None	None		174F	nd		None	Relapser	IFN	<12 IU/ml
7	3	Sof,Vel (12)	None	None	none		93H	None		None	Relapser	IFN	<12 IU/ml
8	2c	Sof,Vel (12)	None	None	31M		31M	None		None	Relapser	Cirrhosis	17 IU/ml
9	2c	Sof,Vel (12)	None	None	None		None	None		None	Relapser	None	<12 IU/ml

Notes: RASs to ongoing therapy and drug regimen-including combination with reduced sensitivity are in Bold; *Previous Interferon treatment.

Abbreviations: Omb, ombitasvir; Par, paritepravir; Das, dasabuvir; RTV, ritonavir; Dac, daclatasvir; Sof, sofosbuvir; Elb, elbasvir; Graz, grazoprevir; Vel, velpatasvir; nd, not done; NEG, not detected.