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Zidovudine Levels in HIV Infected Patients Being Treated for HCV
This study is ongoing, but not recruiting participants.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00059358
  Purpose

This study will test the amount of anti-HIV drugs in the blood cells of HIV-infected patients who are also being treated for hepatitis C virus (HCV) infection.


Condition Intervention Phase
HIV Infections
Hepatitis C
Drug: Ribavirin plus interferon alfa-2b
Drug: Ribavirin
Drug: Peginterferon alfa-2b
Phase I
Phase II

MedlinePlus related topics: AIDS Hepatitis Hepatitis C
Drug Information available for: Zidovudine Ribavirin Interferon alfa-n1 Interferon alfa-2a Interferon alfa-2b Peginterferon Alfa-2b Interferons
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study
Official Title: Pharmacological Interactions Between Zidovudine and Ribavirin in HCV-HIV Co-Infected Patients Treated With Rebetron or Peg-Intron Plus Ribavirin

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Steady state area under the concentration time curve (AUC) between 0 and 12 hours of zidovudine (ZDV)-MP, ZDV-TP, and dTTP in PBMCs from HIV and hepatitis C virus (HCV) coinfected patients before and after peginterferon alfa-2b with or without ribavirin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Systemic exposure (AUC over 0 to 12 hours) of nelfinavir before and after peginterferon alfa-2b with or without ribavirin in HIV and HCV coinfected patients [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Effect of peginterferon alfa-2b with or without ribavirin in HCV RNA viral titers, alanine aminotransferase (ALT) levels, CD4+, and HIV-RNA viral titers in HIV and HCV coinfected patients [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Effect of peginterferon alfa-2b with or without ribavirin on liver histology [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: September 2001
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Participants will begin receive either Rebetron or PEG-Intron plus ribavirin therapy from Weeks 2 through 48
Drug: Ribavirin plus interferon alfa-2b
Oral tablets taken daily
Drug: Ribavirin
Oral tablet taken daily
Drug: Peginterferon alfa-2b
Subcutaneous injection

Detailed Description:

An estimated 50,000 people in Puerto Rico are infected with HCV. HIV and HCV have similar routes of transmission, and HCV co-infection occurs in 8% to 23% of HIV infected patients. Researchers have shown that treatment for HCV with Rebetron (ribavirin plus interferon alfa-2b) significantly decreases HCV viral load without affecting HIV viral load. However, measurements of intracellular levels of the active forms of zidovudine (ZDV-MP and ZDV-TP) were not performed. Such measurements are needed to provide a more rational basis for dosing in HIV/HCV co-infected patients. This study will investigate the intracellular exposure to active ZDV metabolites prior to and after treatment with Rebetron or treatment with PEG-Intron (pegylated interferon) and ribavirin.

Participants in this study will remain on their usual antiretroviral regimen; no changes may be made to that regimen for the first 4 weeks of the study. Upon study entry, participants will have intracellular pharmacokinetic studies. During Week 2, participants will start either Rebetron or PEG-Intron plus ribavirin therapy, will have intracellular pharmacokinetic studies, and will undergo liver biopsy. Additional intracellular pharmacokinetic studies will be performed at Weeks 12 and 24. Rebetron or PEG-Intron plus ribavirin will be given for 48 weeks. A second liver biopsy will be performed 24 weeks after discontinuing Rebetron or PEG-Intron plus ribavirin therapy. Participants will be followed for 72 weeks.

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • HCV-infected
  • HIV-1 infection
  • CD4 cell count > 200 cells/mm³ within 30 days prior to study entry
  • HIV RNA < 400 copies/ml within 90 days of study entry
  • Use of zidovudine, lamivudine, and any PI and/or NNRTI
  • ANC value >= 1,500 ml³ within 30 days of study entry
  • Weight > 50 kg (110 lbs) for women and > 60 kg (132 lbs) for men
  • Acceptable methods of contraception
  • Ability and willingness to complete the Baseline Adherence Questionnaire
  • Documentation of adherence confirmed by the Baseline Adherence Questionnaire and certified by the study officials

Exclusion Criteria

  • Previous ribavirin therapy
  • More than 2 months of interferon therapy
  • Current use of any NRTI other than ZDV and 3TC
  • Hepatitis B surface antigen positive
  • Infectious, autoimmune, tumoral, biliary, or vascular liver disease
  • Alcohol consumption of more than 50 g/day
  • Current use of intravenous drugs
  • Hemoglobin levels < 10 gm/dl
  • Methadone use
  • Chemotherapy
  • Certain medications
  • Acute opportunistic or bacterial infection requiring therapy at the time of enrollment
  • Hemoglobinopathy (e.g., thalassemia) or any other cause of tendency to hemolysis
  • Psychiatric disorders, severe depression, history of suicide attempts, or suicidal ideation
  • Renal disease requiring dialysis
  • Significant coronary diseases or two or more risk factors for coronary diseases, such as > 55 years old, hypertension, and cholesterol > 250 mg/dl
  • Any clinically significant diseases (other than HIV and HCV infection) that, in the opinion of study officials, would compromise the outcome of this study
  • Pregnancy
  • Participation in blinded clinical trial
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00059358

Locations
Puerto Rico
UPR Adult ACTU
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
Investigators
Principal Investigator: Jose F. Rodriguez, PhD MSC-UPR
Principal Investigator: Jorge L. Santana, MD MSC-UPR
  More Information

Click here for more information about peginterferon alfa-2  This link exits the ClinicalTrials.gov site
Click here for more information about ribavirin  This link exits the ClinicalTrials.gov site

Responsible Party: MSC-UPR ( Jose F. Rodriguez, PhD )
Study ID Numbers: 1R01AIA9141-01A1, 5R01AI049141-02
Study First Received: April 23, 2003
Last Updated: September 25, 2008
ClinicalTrials.gov Identifier: NCT00059358  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV
HCV
Ribavirin
Interferon
Co-infection
Treatment experienced

Study placed in the following topic categories:
Interferon-alpha
Sexually Transmitted Diseases, Viral
Liver Diseases
Interferons
Ribavirin
Acquired Immunodeficiency Syndrome
Hepatitis, Viral, Human
Zidovudine
Immunologic Deficiency Syndromes
Hepatitis
Virus Diseases
Digestive System Diseases
HIV Infections
Sexually Transmitted Diseases
Peginterferon alfa-2b
Hepatitis C
Interferon Alfa-2a
Interferon Alfa-2b
Retroviridae Infections

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Flaviviridae Infections
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Infection
Angiogenesis Inhibitors
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses
Lentivirus Infections
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 16, 2009