RBV, a nucleoside analogue, is used for the treatment of hepatitis C virus (HCV) in alliance with interferon-alfa 2a/2b in patients with HIV-1. The mechanism of action of RBV has led to in vitro studies examining the agonism/antagonism in efficacy occurring when used in combination with nucleoside reverse transcriptase inhibitors (NRTIs). The primary objective of the pharmacology component of this current study will be the evaluation of the effect of RBV on the intracellular activation of ZDV or d4T owing to the reported antagonism observed in vitro.

Pharmacokinetic (PK) evaluations for plasma ZDV or d4T and intracellular ZDV or d4T and measurements of their triphosphate anabolites are performed before initial RBV dosing (within 2 weeks of visit) and 8 weeks after RBV administration. Thymidine triphosphate (TTP) concentrations also are quantitated to permit estimation of the ratio of active drug to endogenous triphosphate concentrations.

For entry, prior to RBV dosing, blood samples are collected within 2 hours prior to the ZDV or d4T dose and then at Hours 1, 4, and 8 post dosing. Following the entry PK blood draws, patients initiate RBV treatment within 2 weeks of the first PK study day.

For the Week 8 evaluation (measured as 8 weeks following initiation of RBV), blood samples are collected prior to the ZDV or d4T dose and then at Hours 1, 4, and 8 post dosing.

Inclusion Criteria

Patients may be eligible for this study if they:

• Are at least 13 years of age.
• Have written consent from parent or guardian if under 18 years of age.
• Have HIV infection.
• Have been receiving ZDV or d4T for at least 4 weeks prior to study entry.
• Are planning to receive RBV-containing hepatitis treatment through their doctor or through coenrollment in another ACTG protocol within 2 weeks following entry into the study.
• Have not received RBV for at least 6 months prior to study entry if they were previously treated with RBV.
• Weigh more than 110 pounds (50 kg).

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are pregnant.
• Use rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, or hydroxyurea within 14 days of study entry.
• Abuse alcohol or drugs. Patients in methadone programs may participate.