Zidovudine Levels in HIV Infected Patients Being Treated for HCV

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00059358
First received: April 23, 2003
Last updated: August 6, 2009
Last verified: August 2009
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacological Interactions Between Zidovudine and Ribavirin in HCV-HIV Co-Infected Patients Treated With Rebetron or Peg-Intron Plus Ribavirin

Resource links provided by NLM:


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
Study Completion Date: June 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Additional Information:
No publications provided

Responsible Party: Jose F. Rodriguez, PhD, MSC-UPR
ClinicalTrials.gov Identifier: NCT00059358     History of Changes
Other Study ID Numbers: 1R01AI09141-01A1, 5R01AI049141-02
Study First Received: April 23, 2003
Last Updated: August 6, 2009
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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Hepatitis C
HIV Infections
Infection
Digestive System Diseases
Flaviviridae Infections
Hepatitis
Hepatitis, Viral, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Liver Diseases
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2b
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 30, 2014