Zidovudine Levels in HIV Infected Patients Being Treated for HCV

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Hepatitis C

HIV Infections

Treatments

Drug: Ribavirin plus interferon alfa-2b

Drug: Ribavirin

Drug: Peginterferon alfa-2b

Study type

Interventional

Funder types

NIH

Identifiers

NCT00059358

1R01AI09141-01A1

5R01AI049141-02 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 estimated patients

Sex

All

Ages

21 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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