Chrono-optimal treatments for human immunodeficiency virus/hepatitis C virus co-infection yield comparable survival outcomes with hepatitis C virus mono-infection

Table 1 Baseline characteristics, n (%)

Variables	Before IPTW				After IPTW
	HCV mono-infection (n = 792)	HIV/HCV co-infection (n = 112)	P value	SMD	HCV mono-infection (n = 792)	HIV/HCV co-infection (n = 112)	P value	SMD
Age, years	58.0 (51.0-67.0)	44.0 (36.0-53.5)	< 0.001	0.96	46.0 (37.0-54.0)	44.0 (36.0-53.0)	0.829	0.04
Sex			< 0.001	1.16			0.465	0.09
Male	339 (42.8)	101 (90.2)			691 (87.3)	101 (90.2)
Female	453 (57.2)	11 (9.8)			101 (12.7)	11 (9.8)
Diabetes mellitus			0.35	0.11			0.891	0.02
Absent	685 (86.5)	101 (90.2)			710 (89.7)	101 (90.2)
Present	107 (13.5)	11 (9.8)			82 (10.3)	11 (9.8)
Hypertension			0.187	0.15			0.975	0.004
Absent	657 (86.5)	99 (88.4)			699 (88.3)	99 (88.4)
Present	107 (13.5)	13 (11.6)			93 (11.7)	13 (11.6)
Genotype			< 0.001	0.4			0.428	0.2
1	507 (64.0)	52 (46.4)			430 (54.3)	52 (46.4)
2	233 (29.4)	42 (37.5)			281 (35.5)	42 (37.5)
Others	52 (6.6)	18 (16.1)			81 (10.2)	18 (16.1)
Treatment			< 0.001	0.47			0.808	0.11
None	51 (6.4)	26 (23.2)			151 (19.9)	26 (23.2)
Peginterferon plus ribavirin	212 (26.8)	30 (26.8)			247 (31.2)	30 (26.8)
DAA	529 (66.8)	56 (50.0)			386 (48.8)	56 (50.0)
Liver cirrhosis			< 0.001	0.23			0.109	0.31
Absent	639 (80.7)	96 (85.7)			706 (89.2)	96 (85.7)
Present	153 (19.3)	11 (9.8)			86 (10.8)	11 (9.8)
Unknown	0 (0.0)	5 (4.5)			0 (0.0)	5 (4.5)
Child-Pugh score			0.282	0.16			0.295	0.23
A5	663 (87.8)	34 (81.0)			689 (87.0)	91 (81.1)
A6	65 (9.0)	8 (19.0)			89 (11.2)	15 (13.3)
B7	15 (2.1)	4 (4.3)			10 (1.2)	5 (4.4)
B8	6 (0.8)	1 (1.1)			4 (0.5)	1 (1.1)
B9	2 (0.3)	0 (0.0)			2 (0.2)	0 (0.0)
AFP (ng/mL)	4.6 (2.9-8.4)	2.9 (2.1-5.4)	< 0.001	0.14	4.3 (2.5-6.8)	2.8 (2.0-5.3)	0.253	0.09
ALBI score	-2.8 (-3.0 to -2.5)	-2.8 (-3.1 to -2.5)	0.306	0.05	-2.9 (-3.0 to -2.6)	-2.8 (-3.1 to -2.5)	0.78	0.04
APRI	0.7 (0.4-1.4)	0.7 (0.3-1.3)	0.346	0.04	0.5 (0.3-1.0)	0.7 (0.3-1.3)	0.085	0.23
Fibrosis-4 index	2.4 (1.5-4.2)	1.6 (1.0-2.7)	< 0.001	0.18	1.3 (0.8-2.4)	1.6 (1.0-2.7)	0.23	0.16

IPTW: Inverse probability of treatment weighting; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; DAA: Direct-acting antiviral; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin score; APRI: Aspartate aminotransferase to platelet ratio index.

Table 2 Achievement of sustained virologic response according to treatment in hepatitis C virus mono-infected and human immunodeficiency virus/hepatitis C virus co-infected groups, n (%)

	Not achieved	Achieved
All treated
Before IPTW
HCV mono-infection (n = 741)	49 (6.6)	692 (93.4)
HIV/HCV co-infection (n = 86)	16 (18.6)	70 (81.4)
P value	< 0.001
After IPTW
HCV mono-infection (n = 741)	49 (6.6)	692 (93.4)
HIV/HCV co-infection (n = 86)	11 (13.1)	75 (86.9)
P value	0.114
Treated with Peginterferon plus ribavirin
Before IPTW
HCV mono-infection (n = 212)	42 (19.8)	170 (80.2)
HIV/HCV co-infection (n = 30)	12 (40.0)	18 (60.0)
P value	0.024
After IPTW
HCV mono-infection (n = 212)	42 (19.8)	170 (80.2)
HIV/HCV co-infection (n = 30)	13 (42.9)	17 (57.1)
P value	0.039
Treated with DAA
Before IPTW
HCV mono-infection (n = 529)	7 (1.3)	522 (98.7)
HIV/HCV co-infection (n = 56)	4 (7.1)	52 (92.9)
P value	0.015
After IPTW
HCV mono-infection (n = 529)	7 (1.3)	522 (98.7)
HIV/HCV co-infection (n = 56)	2 (3.7)	54 (96.3)
P value	0.139

IPTW: Inverse probability of treatment weighting; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; DAA: Direct-acting antiviral.

Table 3 Cox regression analysis of factors associated with overall survival of hepatitis C virus after inverse probability of treatment weighting in patients who achieved sustained virologic response

Variables	Crude HR (95%CI)	P value	Adjusted HR (95%CI)	P value
Group		0.360		0.280
HCV mono-infection	1 (reference)		1 (reference)
HIV/HCV co-infection	0.37 (0.05-3.07)		0.46 (0.11-1.91)
Age (year)		0.002		0.009
< 65	1 (reference)		1 (reference)
≥ 65	3.35 (1.54-7.30)		2.45 (1.21-4.96)
Sex		0.288
Male	1 (reference)
Female	0.68 (0.33-1.39)
Diabetes mellitus		0.002		0.042
Absent	1 (reference)		1 (reference)
Present	3.11 (1.54-6.27)		2.04 (1.03-4.05)
Hypertension		0.104
Absent	1 (reference)
Present	0.35 (0.10-1.24)
Child-Pugh score		0.804
A	1 (reference)
B	1.02 (0.90-1.14)
Treatment		0.035		0.184
Peginterferon plus ribavirin	1 (reference)		1 (reference)
DAA	2.76 (1.07-7.09)		1.95 (0.74-5.15)
Fibrosis-4 index		< 0.001		0.649
≤ 3.25	1 (reference)		1 (reference)
> 3.25	1.26 (1.24-1.97)		1.13 (0.67-1.93)
Liver cirrhosis		< 0.001		0.005
Absent	1 (reference)		1 (reference)
Present	5.18 (2.81-9.55)		2.72 (1.34-5.52)
AFP (ng/mL)		0.580
< 20	1 (reference)
≥ 20	1.04 (0.91-1.17)
ALBI score		< 0.001		0.039
≤ -2.60	1 (reference)		1 (reference)
> -2.60	3.55 (1.82-6.91)		1.97 (1.04-3.73)
APRI		0.026		0.791
< 1	1 (reference)		1 (reference)
≥ 1	2.21 (1.10-4.44)		1.10 (0.54-2.25)

HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; DAA: Direct-acting antiviral; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin score; APRI: Aspartate aminotransferase to platelet ratio index; HR: Hazard ratio; 95%CI: 95% confidence interval.

Table 4 Cox regression analysis of factors associated with time-to-occurrence of hepatitis C virus after inverse probability of treatment weighting in patients who achieved sustained virologic response

Variables	Crude HR (95%CI)	P value	Adjusted HR (95%CI)	P value
Group		0.113		0.144
HCV mono-infection	1 (reference)		1 (reference)
HIV/HCV co-infection	0.19 (0.02-1.48)		0.22 (0.03-1.69)
Age (year)		0.692
< 65	1 (reference)
≥ 65	1.21 (0.47-3.13)
Sex		0.200
Male	1 (reference)
Female	0.58 (0.25-1.34)
Diabetes mellitus		0.034		0.107
Absent	1 (reference)		1 (reference)
Present	2.44 (1.07-5.58)		1.81 (0.88-3.73)
Hypertension		0.217
Absent	1 (reference)
Present	1.72 (0.73-4.08)
Child-Pugh score		0.922
A	1 (reference)
B	1.01 (0.89-1.14)
Treatment		0.507
Peginterferon plus ribavirin	1 (reference)		1 (reference)
DAA	1.31 (0.59-2.94)		1.95 (0.74-5.15)
Fibrosis-4 index		0.016		0.736
≤ 3.25	1 (reference)		1 (reference)
> 3.25	1.41 (1.07-1.86)		1.08 (0.68-1.73)
Liver cirrhosis		0.002		0.004
Absent	1 (reference)		1 (reference)
Present	3.80 (1.63-8.85)		2.54 (1.35-4.77)
AFP (ng/mL)		0.758
< 20	1 (reference)
≥ 20	0.98 (0.87-1.11)
ALBI score		0.149
≤ -2.60	1 (reference)
> -2.60	1.83 (0.81-4.14)
APRI		0.015		0.068
< 1	1 (reference)		1 (reference)
≥ 1	3.33 (1.26-8.77)		2.13 (0.95-4.80)

HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; DAA: Direct-acting antiviral; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin score; APRI: Aspartate aminotransferase to platelet ratio index; HR: Hazard ratio; 95%CI: 95% confidence interval.