Zidovudine Levels in HIV Infected Patients Being Treated for HCV

NCT ID: NCT00059358

Last Updated: 2009-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-09-30
• Study Completion Date: 2005-06-30

Brief Summary

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.

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.

Conditions

HIV Infections; Hepatitis C

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Participants will begin receive either Rebetron or PEG-Intron plus ribavirin therapy from Weeks 2 through 48

Group Type: EXPERIMENTAL

Ribavirin plus interferon alfa-2b

Intervention Type: DRUG

Oral tablets taken daily

Ribavirin

Intervention Type: DRUG

Oral tablet taken daily

Peginterferon alfa-2b

Intervention Type: DRUG

Subcutaneous injection

Interventions

Ribavirin plus interferon alfa-2b

Oral tablets taken daily

Intervention Type: DRUG

Ribavirin

Oral tablet taken daily

Intervention Type: DRUG

Peginterferon alfa-2b

Subcutaneous injection

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

MSC-UPR

Principal Investigators

Jose F. Rodriguez, PhD

Role: PRINCIPAL_INVESTIGATOR

MSC-UPR

Jorge L. Santana, MD

Role: PRINCIPAL_INVESTIGATOR

MSC-UPR

Locations

UPR Adult ACTU

San Juan, , Puerto Rico

Countries

Puerto Rico

Other Identifiers

5R01AI049141-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01AI09141-01A1

Identifier Type: -

Identifier Source: org_study_id