Zidovudine Levels in HIV Infected Patients Being Treated for HCV

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.

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