Retreatment With High Doses of pegIFN Alfa-2a and Ribavirin of Previous Nonresponders HIV-coinfected Patients With Cirrhosis Due to HCV 1-4

Sociedad Andaluza de Enfermedades Infecciosas

Status and phase

Completed

Phase 3

Phase 2

Conditions

Liver Cirrhosis

HIV Infection

Hepatitis C Virus

Treatments

Drug: Pegylated interferon alfa-2a and Ribavirin

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT01006031

HEPAVIR_IFN_2009

Details and patient eligibility

About

Objective: To evaluate the efficacy and safety of high doses of both peginterferon-alfa 2a (360 ug per week) plus ribavirin (800 mg b.i.d.) in HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(*) to a standard dose treatment of both drugs.

(*) Non previous virological response: no decrease of plasma RNA-HCV at least 2 log10 after 12 weeks in treatment or breakthrough viremia while on treatment.

Additionally, this study will evaluated the influence of simultaneous peginterferon-alfa 2a and ribavirin plasma concentrations on early viral response (EVR) and sustained viral response (SVR) in these patients.

Method: Pilot clinical trial, phase II-III, open labeled multicenter in which patients from several hospitals of the Servicio Andaluz de Salud will be enrolled.

The usual clinical and analytical follow up will be performed but additional blood samples will be obtained for determination of interferon and ribavirin plasma levels. The primary end point will be a sustained virologic response (defined as an undetectable serum HCV-RNA after 24 weeks after the cessation of treatment). Likewise, rapid virological response (at 4 weeks of treatment), early virological response (at 12 weeks), and end of treatment response rates will be evaluated as well as their relationships with the plasma interferon an ribavirin concentrations determined by ELISA and HPLC, respectively. The safety and tolerability of the studied medications will be evaluated by means of clinical adverse events, physical examination and laboratory results. The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age older than 18 years
HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(*) to a standard dose treatment of both drugs.
Women of child-bearing age: negative pregnancy test
Ability to understand and sign a written consent form

Exclusion criteria

HCV genotypes different to 1 or 4
Acute or chronic hepatitis B infection (positivity for hepatitis B surface antigen or plasma DNA) or other concomitant causes of liver disease
Pregnancy or breast feeding.
Decompensated liver disease at baseline.
Neutropenia <1000/uL, anemia <100 g/L or thrombocytopenia <20.000/uL.
Creatinine clearance < 50 mL/min.
Concomitant treatment with immunomodulators or zidovudine, didanosine or stavudine.
Organ or bone marrow transplantation
Current alcoholism or iv drug abuse. Methadone is allowed.
Current neoplasm and/or anti-tumor chemotherapy or immunomodulators
Psychosis or uncontrolled clinical depression
Auto-immune disease, including auto-immune hepatitis
History of significant cardiovascular disease (NYHA III-IV) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure.
Thyroid dysfunction.
Clinically significant retinal abnormalities
Inability to understand and sign a written consent form