Zidovudine Levels in HIV Infected Patients Being Treated for HCV

August 6, 2009 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Pharmacological Interactions Between Zidovudine and Ribavirin in HCV-HIV Co-Infected Patients Treated With Rebetron or Peg-Intron Plus Ribavirin

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

16

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • UPR Adult ACTU

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Throughout study
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
Throughout study
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
Through Week 48
Effect of peginterferon alfa-2b with or without ribavirin on liver histology
Time Frame: At Week 72
At Week 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Jose F. Rodriguez, PhD, MSC-UPR
  • Principal Investigator: Jorge L. Santana, MD, MSC-UPR

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2001

Primary Completion (Actual)

June 1, 2005

Study Completion (Actual)

June 1, 2005

Study Registration Dates

First Submitted

April 23, 2003

First Submitted That Met QC Criteria

April 23, 2003

First Posted (Estimate)

April 24, 2003

Study Record Updates

Last Update Posted (Estimate)

August 7, 2009

Last Update Submitted That Met QC Criteria

August 6, 2009

Last Verified

August 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01AI09141-01A1
  • 5R01AI049141-02 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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