Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study

Figures & data

Figure 1 Flow chart.

Table 1 Baseline demographics and clinical characteristics

	N (%), n = 64
Age, year, median [IQR]	49 [46–52]
Gender, male	48 (75%)
Ethnicity, non-black	61 (95%)
IVDU	47 (73%)
BMI ≥25 kg/m^2	18 (28%)
Response to previous HCV treatment
Relapse	20 (31%)
Breakthrough	5 (8%)
Partial response	18 (28%)
Null response	21 (33%)
CDC stage C	14 (22%)
CD4, cells/mm^3, median [IQR]	728 [527–923]
Nadir <200/mm^3	35 (55%)
HIV-RNA <50 copies/mL	61 (95%)
Antiretroviral treatment
2 NRTIs* + ATV/r	32 (50%)
2 NRTIs+RAL	27 (42%)
Other**	5 (8%)
HCV genotype
1a	50 (78%)
1b	14 (22%)
HCV-RNA, log IU/mL, median [IQR]	6.4 [5.9–6.7]
HCV-RNA >800 000 IU/mL	49 (77%)
HOMA (n = 54), median [IQR]	3.2 [1.9–6.2]
> 2.5	36 (67%)
IL28B genotype (n = 63)
CC	22 (35%)
CT	31 (49%)
TT	10 (16%)
Fibrosis score
F0/F1	21 (33%)
F2	18 (28%)
F3	14 (22%)
F4	11 (17%)

* NRTIs: TDF + FTC = 57; ABC + 3TC = 2;

** Other ART regimens: TDF + ATV/r + RAL = 2; FTC + ATV/r + RAL = 1; TDF + FTC + ATV/r + RAL = 1; TDF + FTC + ATV + RAL = 1 Data are n (%) unless otherwise specified. IQR = Inter Quartile Range. IVDU = Intra-Venous-Drug-Use. BMI = Body-Mass Index. HCV = Hepatitis C Virus. CDC = Center for Diseases Control. NRTI = Nucleoside Reverse Transcriptase Inhibitor. ABC = abacavir. ATV = atazanavir. ATV/r = ritonavir- boosted atazanavir. FTC = emtricitabin. 3TC = lamivudin. RAL = raltegravir. TDF = tenofovir. HOMA = Homeostasis Model Assessment. IL28B = Interleukin-28B.

Table 2 SVR₂₄ rate according to baseline characteristics, week 4 and week 8 virological responses, ribavirin C_trough at week 4 and BOC C_trough at week 8

		SVR24 n = 34	No SVR24 n = 30	p-value*
Age	< 50 years	19 (52.8%)	17 (47.2%)	0.9497 (a)
	≥ 50 years	15 (53.6%)	13 (46.4%)
Gender	Male	24 (50.0%)	24 (50.0%)	0.3855 (a)
	Female	10 (62.5%)	6 (37.5%)
Ethnicity	Black	2 (66.7%)	1 (33.3%)	1.0000 (b)
	Non-black	32 (52.5%)	29 (47.5%)
IVDU	Yes	23 (48.9%)	24 (51.1%)	0.2642 (a)
	No	11 (64.7%)	6 (35.3%)
BMI	< 25 kg/m^2	23 (50.0%)	23 (50.0%)	0.4232 (a)
	≥ 25 kg/m^2	11 (61.1%)	7 (38.9%)
Response to previous HCV treatment	Relapse	18 (90.0%)	2 (10.0%)	<0.0001 (b)
	Breakthrough	0 (0.0%)	5 (100.0%)
	Partial response	11 (61.1%)	7 (38.9%)
	Null response	5 (23.8%)	16 (76.2%)
CDC stage	A/B	26 (52.0%)	24 (48.0%)	0.7332 (a)
	C	8 (57.1%)	6 (42.9%)
CD4, cells/mm^3	<350	3 (60.0%)	2 (40.0%)	1.0000 (b)
	≥350	31 (52.5%)	28 (47.5%)
Antiretroviral treatment (n = 59)	2 NRTIs + ATV/r	13 (40.6%)	19 (59.4%)	0.0223 (a)
	2 NRTIs + RAL	19 (70.4%)	8 (29.6%)
HCV genotype	1a	23 (46.0%)	27 (54.0%)	0.0309 (a)
	1b	11 (78.6%)	3 (21.4%)
HCV-RNA, log IU/mL	<6.4	21 (65.6%)	11 (34.4%)	0.0451 (a)
	≥6.4	13 (40.6%)	19 (59.4%)
HOMA (n=54)	≤2.5	5 (27.8%)	13 (72.2%)	0.0209 (a)
	>2.5	22 (61.1%)	14 (38.9%)
IL28B genotype (n = 63)	CC	12 (54.5%)	10 (45.5%)	0.7897 (a)
	CT	15 (48.4%)	16 (51.6%)
	TT	6 (60.0%)	4 (40.0%)
Fibrosis score	F0-F2	22 (56.4%)	17 (43.6%)	0.5107 (a)
	F3-F4	12 (48.0%)	13 (52.0%)
HCV-RNA decrease at W4 (n = 62)	<1 log	13 (38.2%)	21 (61.8%)	0.0038 (a)
	≥1 log	21 (75.0%)	7 (25.1%)
HCV-RNA-W8	Undetectable	15 (93.8%)	1 (6.3%)	0.0002 (a)
	Detectable	19 (39.6%)	29 (60.4%)
RBV-Ctrough-W4 (μg/mL) (n = 59)	<2	17 (41.5%)	24 (58.5%)	0.0296 (a)
	≥2	13 (72.2%)	5 (27.8%)
BOC-Ctrough-W8 (μg/L) (n = 41)	<127	9 (45.0%)	11 (55.0%)	0.6365 (a)
	≥127	11 (52.4%)	10 (47.6%)

* Χ² test (a) or Fisher exact test (b) Data are n (%) unless otherwise specified; IVDU = Intra-Venous-Drug-Use. CDC = Center for Diseases Control. NRTI = Nucleoside Reverse Transcriptase Inhibitor. ATV/r = ritonavir-boosted atazanavir. RAL = raltegravir. HCV = Hepatitis C Virus. HOMA = Homeostasis Model Assessment. RBV = ribavirin. BOC = Boceprevir.

Table 3 Resistance profile in patients with virological failure

Patient	Response to previous treatment	HCV genotype	Baseline mutations	Time of failure	log HCV-RNA (IU/mL)	Emerging mutations	Reason for therapy discontinuation
1	Null responder	1a	WT	W12	7,41	V36 M, R155 K	Patient’s decision
2	Null responder	1a	WT	W16	7,12	V36 M, R155 K	Virologic failure
3	Null responder	1a	WT	W8	6,39	V36 V/M, R155R/T/K	Virologicfailure
4	Breakthrough	1a	WT	W8	5,57	V36 V/A, T54T/A, R155R/K, I170I/V	Virologic failure
5	Null responder	1a	WT	W8	5,88	R155 K	Patient’s decision
6	Null responder	1a	WT	W8	6,36	V36 V/M	Virologic failure
7	Null responder	1b	WT	W28	6,7	T54S, A56S, I170 V	Virologic failure

All patients had wild type at baseline.

WT = wild type.

Table 4 Pharmacokinetic parameters of ritonavir-boosted atazanavir, raltegravir, and boceprevevir

	AUC0–8 h (μg/L.h)	p-value	Ctrough (μg/L)	p-value	Cmax (μg/L)	p-value
ATV/r -BL	13212 ± 6620	<0.01	764 ± 754	NS^(2)	2413 ± 1514	NS^(2)
ATV/r -W8 with BOC^(1)	6533 ± 3178		508 ± 486		1418 ± 793
RAL –BL	5901 ± 6167	<0.01	338 ± 348	NS^(2)	1387 ± 1478	NS^(2)
RAL-W8 with BOC^(1)	9249 ± 3032		154 ± 115		3556 ± 1408	–
BOC-W8 with ATV/r^(3)	4170 ± 1048	NS^(2)	154 ± 89.2	NS^(2)	1315 ± 458	NS^(2)
BOC-W8 with RAL^(3)	5310 ± 2643	NS^(2)	118 ± 79.5	NS^(2)	1040 ± 574	NS^(2)

⁽¹⁾ ATV/r and RAL mean PK parameters were compared between baseline and W8.

⁽²⁾ NS: not statistically significant; BL: Baseline.

⁽³⁾ BOC mean PK parameters were compared with published data [29].