Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance

Inclusion Criteria

For Step 1:

• HIV infected
• Exhibited no response to previous treatment with PEG-IFN alfa-2a 180 mcg/week or alfa-2b 1.5 mcg/kg/week and at least 1000 mg/day ribavirin given for at least 12 consecutive weeks. More information on this criterion can be found in the protocol.
• HOMA-IR valued greater than 2.5 within 42 days prior to study entry. More information on this criterion can be found in the protocol.
• CD4 count of at least 200 cells/mm3 within 42 days prior to study entry
• HCV RNA of at least 60 IU/ml by quantitative RT-PCR assay with or without reactive anti-HCV antibodies within 42 days prior to study entry
• Documentation of infection with HCV genotype 1, within 42 days prior to study entry
• On stable or no antiretroviral therapy for 12 weeks prior to study entry. Interruptions in treatment lasting 14 days or less are allowed if the participant reinitiated the same regimen prior to study entry. Dose modifications or changes in drug formulations during the 12 weeks prior to study entry are permissible.
• Participants on antiretroviral therapy should plan to remain on the same therapy for at least 24 weeks after study entry. Participants not on antiretroviral therapy should have no plans to initiate therapy during the first 24 weeks following study entry.
• Participants with documented or suspected hepatic cirrhosis must have a modified Child-Pugh-Turcotte (CPT) within 42 days prior to study entry.
• Participants with documented or suspected hepatic cirrhosis must have either serum alpha-fetoprotein level of 50 ng/ml or less within 24 weeks prior to study entry; OR serum alpha-fetoprotein greater than 50 ng/ml but no greater than 400 ng/ml with an imaging procedure that shows no evidence of a hepatic tumor, both obtained within 24 weeks prior to study entry.
• Certain laboratory values obtained within 42 days prior to study entry. More information on this criterion can be found in the protocol.
• Willing to use effective forms of contraception throughout the study. More information on this criterion can be found in the protocol.
• Ability and willingness of participant to give written informed consent.

For Step 2:

• No more than 28 days have passed since the Step 1, Week 24 visit
• Participants who were treated in Step 1 who meet the following criteria:
• Detectable HCV RNA (> 60 IU/mL) at the Step 1, Week 24 evaluation
• CD4 cell count of at least 200 cells/mm3 at Week 24. If the CD4 count is less than 200 cells/mm3 at Week 24, then it must not have decreased by more than 20 cells/mm3 from the Step 1 entry value.
• Taking pioglitazone at the time of Step 2 entry
• Certain laboratory values obtained within 28 days prior to Step 2 entry. More information on this criterion can be found in the protocol.
• Willing to use an effective form of contraception throughout the study
• Female participants of reproductive potential are required to have a negative serum or urine β-HCG pregnancy test within 14 days prior to Step 2 entry
• Participants without a pregnant partner.

Exclusion Criteria

• Presence of known causes of significant liver disease. More information on this criterion can be found in the protocol.
• Evidence of decompensated liver disease manifested by presence or history of ascites, variceal bleeding, or hepatic encephalopathy
• History of HCV treatment within 28 days prior to study entry
• Evidence that nonresponse to prior HCV treatment may have been due to nonadherence or certain dose reductions. More information on this criterion can be found in the protocol.
• Use of interferon gamma, TNF-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, or hydroxyurea within 14 days prior to study entry
• Current use of didanosine or zidovudine or plans to initiate use of either during the study
• Active drug or alcohol abuse or dependence that, in the opinion of the study investigator, could interfere with adherence to study requirements
• History of uncontrolled