zidovudine levels in hiv infected patients being treated for hcv

Conditions: HIV Infections; Hepatitis C

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.

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.

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

Keywords: hiv hcv ribavirin interferon co-infection treatment experienced