Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Table 1 Baseline assessment before starting treatment in HCV-HIV co-infected patients

Assessment of liver diseases status

CTP staging

HCV-RNA

HCV genotype

AFP and USG/CT scan for HCC

HBV markers (HBsAg and anti-HBc)

HBV-DNA for patients with isolated anti-HBc to detect low level viremia

Anti-HAV IgG

Assessment of HIV disease status

Current and past opportunistic infections

HIV-associated malignancy

CD4 count

HIV viral load

Details of HAART

Assessment for problems precluding therapy or requiring control before therapy

TSH

Screening for depression or other psychiatric diseases

Complete blood count

Blood sugar

History of significant cardiac, renal, or pulmonary disease

Fundus examination for retinopathy

Beta HCG to exclude pregnancy in females

Urine toxicology screening to exclude concurrent active substance abuse

Social support and treatment compliance

HIV: Human immunodeficiency virus; HCV: Hepatitis C virus; CTP: Child Turcotte Pugh; AFP: α-feto protein; USG: Ultrasonogram; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HCC: Hepatocellular cancer; HAART: Highly active antiretroviral therapy; TSH: Thyroid stimulating hormone; HCG: Human chorionic gonadotropin.

Table 2 Trials of anti-HCV treatment in HIV patients

Author (yr)	Country	n	Schedule	Duration	Overall response (%)		GT-2/3		GT-1/4
					ETR	SVR	ETR	SVR	ETR	SVR
Pérez-Olmeda et al[39] (2003)	Spain	68	PEG-IFN 150 μg/wk × 12 wk, then 100 μg/wk + RBV 400 mg bid	6 mo for GT-1/4 and 12 mo for GT-3	30.3	24.2	811	52.3	30.3	24.2
Cargnel et al[40] (2005)	Italy Multi Center	135	PEG-IFN 1.5 μg/kg per week + RBV 400 bid	48 wk	28.9	21.7	43.7	34.4	18.7	9.4
			PEG-IFN 1.5 μg/kg per week		16.7	9.1	16.2	10.8	14.7	8.8
Bräu et al[41] (2004)	United States	107	IFN α-2b 3 mu tiw + RBV 800 mg /d vs	48 wk	18.9	11.3	50	41.7	10	2.5
			IFN α 2b 3 mu tiw + placebo × 16 wk, then RBV 800 mg/d		7.4	5.6
Laguno et al[42] (2004)	Spain	95	IFN α 2b 3 mu tiw + RBV 800-1200 mg/d vs	48 wk for GT-¼ and 24 wk for HT-2/3	301	211	67	47	11	7
			PEG-IFN 100-150 μg/wk + RBV 800-1200 mg/d		52	44	68	53	41	38
Myers et al[43] (2004)	Canada	32	PEG-IFN α 2b (1.5 μg/kg per week) + weight based RBV (1000 mg for 75 kg or less or 1200 mg for > 75 kg) in IFN non responders	48 wk	19	16		29		9
Chung et al[44] (2004) ACTG	United States	133	PEG-IFN α 2a 180 μg/wk + RBV (400 mg/d × 4 wk- 600 mg/d × 4 wk - 1000 mg/d vs	48 wk	411	271	801	731	331	29
			IFN α 2a 6 mu tiw × 12 wk, then 3 mu tiw +RBV as above		12	12	33	33	6	6
Moreno et al[45] (2004)	Spain	35	PEG-IFN 50 μg/wk + RBV 800 mg/d	48 wk		31		70		25
Torriani et al[46] (2004)	APRICOT	868	PEG-IFN α 2a 180 μg/wk + RBV 800 mg/d vs	48 wk	47	401	64	621	38	29
			PEG-IFN α 2a + Placebo vs		31	20	57	36	21	14
			IFN α 2a 3 mu tiw + RBV		14	12	27	20	8	7
Carrat et al[47] (2004) RIBAVIC	France Multi Center	412	PEG-IFN α 2b 1.5 μg/kg per week + RBV 800 mg/d vs	48 wk	351	271	50	43.7	25.6	16.81
			IFN α 2b 3 mu tiw + RBV 800 mg/d		21	20	47.4	43.4	6.2	6.2
Khalili et al[48] (2005)	United States	154	PEG-IFN α 2a 180 μg/wk	48 wk	55	35	NA
			PEG-IFN + Placebo		3	0
			PEG-IFN + RBV 800 mg/d		11	5
Hopkins et al[49] (2006)	United Kingdom	45	PEG-IFN α 2b 1.5 μg/kg per week + RBV (1000-1200 mg/d)	24 wk for GT- 2/3 and 48 wk for GT-1	62	53	82	751	25	19
Moreno et al[50] (2006)	Spain	70 (HCV)	PEG-IFN α 2b 1.5 μg/kg per week + RBV 10.6 mg/kg per day	48 wk	46	371	All patients had GT-1 or 4 infection and the overall ETR and SVR were 39 and 30% respectively
		36 (HCV +HIV)			25	171
Santin et al[51] (2006)	Spain Multi Center	60	PEG-IFN α 2b 80-150 μg/wk + RBV 800-1200 mg/d	24 wk for GT 2/3 and 48 wk for GT ¼	33	27	53	42	24	201
Voigt et al[52] (2006)	Germany Multi Center	122	PEG-IFN α 2b 1.5 μg/kg per week + RBV 800 mg/d	24 wk for GT 2/3 and 48 wk for GT ¼	52	25	72	44	41	181
Fuster et al[53] (2006)	Spain Multi Center	110	PEG-IFN 180 μg/wk + RBV 800 mg/d	24 wk for GT 2/3 and 48 wk for GT ¼	53	42	68	55	47	33
Righi et al[54] (2008)	Italy	43	PEG-IFN 2a 180 μg/wk or 2b 1.5 μg/kg per week + RBV (10.6 mg/kg per day)	24 wk for GT 3 and 48 wk for GT-1a	51	30		38		24

¹Responses are on intent to treat analysis. ETR: End of treatment response (HCVRNA < 50 copies/mL); SVR: Sustained virologic response (HCVRNA < 50 copies/mL 6 mo after discontinuing treatment); PEG-IFN: Pegylated interferon; RBV-ribavirin; GT: Genotype; tiw: Three times a week; ACTG: AIDS clinical trial group; APRICOT: AIDS pegasys ribavirin international coinfection trial.

Table 3 Barriers against anti-HCV therapy in co-infected patients

Patient-related factors

Active substance abuse

Concern regarding adverse effects

Cost of treatment

Lack of social support

Lack of transport

Number of pills and dosing frequency (including HAART)

Physician-related factors

Lack of experience

Lack of awareness

Lack of motivation for referral

Fear of adverse effects

HAART: Highly active anti-retroviral therapy.

Table 4 Morbidity and mortality with PEG-IFN + RBV: results of three large trials

Parameter	Sub-parameter	ACTG (n = 66)	APRICOT (n = 286)	RIBAVIC (n = 194)
Treatment related adverse events	Influenza like symptoms	31 (47)		172 (89)
	Fatigue		128 (44)
	Pyrexia		128 (44)
	Headache		111 (39)
	Myalgia		103 (36)
	Nausea		85 (30)
	Diarrhea		81 (28)
	Depression	7 (11)	76 (26)	46 (24)
	Weight loss		82 (28	46 (24)
	Injection site reaction			44 (21)
	Anorexia			38 (20)
	Irritability			32 (16)
	Bronchitis/cough			26 (13)
	Insomnia		76 (26)	19 (10)
	Elevated lipase/amylase	9 (14)
	Glucose: high or low	19 (28)
HIV-related adverse events	Lipodystrophy			37 (19)
	Oral candidiasis		2 (< 1)	30 (15)
	AIDS defining event		2 (< 1)
Specific serious adverse events	Psychiatric disorders			8 (4)
	Liver failure		1 (< 1)	4 (2)
	Liver decompensation		5 (2)
	Pneumonia/sepsis		2 (1)	6 (3)
	Symptomatic increased lactate		4 (1)	9 (5)
	Pancreatitis		2 (1)
	Lactic acidosis	0 (0)	2 (1)
	ELAT > 10 ULN	20 (30)		16 (8)
	Neutropenia < 500/μL	5 (8)		10 (5)
	Anemia	2 (3)	6 (2)
	Thrombocytopenia	1 (2)	1 (< 1)
	Drug abuse		4 (1)
	Deep vein thrombosis		3 (1)
	Bacterial infection		3 (1)
	Gastroenteritis		2 (1)
Any serious event	Total		50 (17)	68 (35)
	Treatment-related		24 (8)	30 (15)
Deaths	Total	1 (2)	4 (1)	5 (3)

Table 5 Hepatotoxicity of highly active anti-retroviral therapy drugs and guidelines for their use in patients with liver disease

Group	Drug	Dose adjustment
NRTI	Didanosine	Use cautiously
NNRTI	Delavirdine, Efavirenz, Nevirapine	Caution with hepatic impairment
PIs	Lopinavir, Nelfinavir, Ritonavir, Saquinavir	Caution with hepatic impairment
	Atazanavir	Reduce 25% of dose in patients with CTP stage B and C
	Indinavir	Reduce dose by 25% in CTP stage B and C
	Tipranavir	Avoid in patients with CTP stage B or C
	Fosamprenavir	Avoid in patients with CTP stage C
	Darunavir	Avoid in patients with CTP stage C

Table 6 Recommendations for management of HCV in HIV patients

All HIV patients should be screened for concomitant HCV infection

Effective management of HCV is crucial to improve the survival of HIV patients

Patients with stage 2 or more disease are candidates for therapy provided their HIV disease is controlled

Pegylated interferon and weight based ribavirin combination is recommended

Liver transplantation is no longer a contra-indication in the presence of HIV and should be considered in appropriate patients

Patients with cirrhosis should be screened for esophageal varices and for hepatocellular carcinoma