Zidovudine Levels in HIV Infected Patients Being Treated for HCV

National Institute of Allergy and Infectious Diseases (NIAID)16 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infections Hepatitis C

Interventions

Ribavirin plus interferon alfa-2bDRUG

Oral tablets taken daily

RibavirinDRUG

Oral tablet taken daily

Peginterferon alfa-2bDRUG

Subcutaneous injection

Eligibility

Sex: ALLMin age: 21 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (1)

UPR Adult ACTU

San Juan, Puerto Rico

Outcomes

Primary Outcomes

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

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

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

Effect of peginterferon alfa-2b with or without ribavirin on liver histology

Time frame: At Week 72

Data from ClinicalTrials.gov

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