A Comparison of the Effectiveness, Safety, and Tolerability of Two Different Hepatitis C Treatments in Patients Infected With Both HIV and Hepatitis C Virus (HCV)
Condition: HIV Infections; Hepatitis C
MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to see if treatment with PEG-interferon-alfa-2a (PEG-IFN) plus
      ribavirin is a more effective treatment for hepatitis C virus (HCV) than interferon-alfa-2a
      (IFN) plus ribavirin for patients infected with both HCV and HIV. The study will also compare
      the 2 regimens to see which has fewer side effects.

      HCV infection is common in patients infected with HIV. Patients infected with both HIV and
      HCV viruses seem to have more severe hepatitis C. A combination of IFN and ribavirin has been
      shown to lessen the severity of HCV. PEG-IFN is a modified form of IFN that stays in the
      blood longer, which means that patients would not have to take the treatment as often. This
      study will compare the safety and effectiveness of PEG-IFN to IFN when each is combined with
      ribavirin.
    

Detailed description: 
      Infection with HCV is common in patients infected with HIV owing to similar routes of
      transmission. The cellular immunosuppression caused by HIV infection appears to lead to an
      increased HCV plasma load, more progressive liver disease, and, in patients with chronic
      hepatitis C, increased mortality. Ribavirin treatment combined with IFN has shown improved
      sustained virologic response rates over IFN monotherapy. PEG-IFN, a chemically modified
      formulation of IFN, circulates for a much longer time in the blood than the parent compound.
      Pharmacokinetic and pharmacodynamic data suggest that PEG-IFN injected weekly would have the
      potential for superior efficacy as compared with IFN injected 3 times per week. The efficacy
      and safety profiles of combination therapy with PEG-IFN and ribavirin are not well known.
      This study will compare combination therapy consisting of PEG-IFN and ribavirin with that of
      IFN and ribavirin.

      Patients are stratified according to HCV genotype and CD4 count and viral load, then
      randomized to either Arm A (IFN plus ribavirin) or Arm B (PEG-IFN plus ribavirin). Patients
      receive up to 48 weeks of treatment. Virologic response is assessed at Week 24 and a decision
      to continue or discontinue treatment is made. If a virologic response is shown at Week 24,
      the patient continues treatment for an additional 24 weeks. If no virologic response is
      observed, then the histologic response is assessed by a liver biopsy. If biopsy shows a
      histologic response is present, treatment is continued for 24 weeks. If biopsy shows no
      histologic response, treatment is discontinued. [AS PER AMENDMENT 07/20/01: Patients with
      virologic response who discontinue after Week 24 will have liver biopsy at time of
      discontinuation. Patients with no virologic response continuing study treatment after having
      a liver biopsy within 2 weeks of Week 24, who also demonstrate histologic response and decide
      to discontinue after Week 24, are strongly encouraged to have a 2nd liver biopsy at the end
      of treatment. Patients with no virologic response who discontinue after Week 24 will not have
      liver biopsy at time of discontinuation.] Physical examinations are done regularly and blood
      samples collected for routine laboratory tests, confidential genetic testing, and to measure
      HCV and HIV-1 plasma viral loads. Women able to become pregnant have regular pregnancy tests.
      All patients are followed for an additional 24 weeks after treatment discontinuation.

      Patients may enroll in 1 or none of the following substudies: A5091s, Hepatic C Viral
      Kinetics in Subjects Co-infected with Human Immunodeficiency Virus-1 (HIV-1) and Hepatitis C
      Virus Genotype 1 (HCV-1); [AS PER AMENDMENT 07/20/01: The following text has been deleted: or
      A5092s, Evaluation of the Effects of Ribavirin on Zidovudine (ZDV) or Stavudine (d4T)
      Triphosphate Formation] [AS PER AMENDMENT 07/20/01: Substudy A5092s, Evaluation of the
      Effects of Ribavirin on Zidovudine (ZDV) or Stavudine (d4T) Triphosphate Formation is now a
      stand-alone study.]
    

Intervention name(s): Ribavirin; Interferon alfa-2a; Peginterferon alfa-2a
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Primary purpose: Treatment
Keywords: Ribavirin; Polyethylene Glycols; Interferon Alfa-2a; HIV-1; Antiviral Agents; Hepatitis C, Chronic