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 less than 60 IU/ml by quantitative RT-PCR assay with or without reactive anti-HCV antibodies within 42 days prior to study entry
• Infection with HCV genotype 1, within 180 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 more are allowed if the patient 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.
• Patients on antiretroviral therapy should plan to remain on the same therapy for at least 24 weeks after study entry. Patients not on antiretroviral therapy should have no plans to initiate therapy during the first 24 weeks following study entry.
• Patients 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 AND modified Child-Pugh-Turcotte (CPT) within 42 days 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

For Step 2:

• No more than 28 days have passed since the Step 1, Week 24 visit

• Patients who were treated in Step 1 who meet the following criteria:

  1. Detectable HCV RNA at the Step 1, Week 24 evaluation
  2. 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.
  3. Taking pioglitazone at the time of Step 2 entry
• Certain laboratory values obtained within 28 days prior to study entry. More information on this criterion can be found in the protocol.
• Willing to use an effective form of contraception throughout the study

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 seizure disorder
• Uncontrolled depression or other psychiatric disorder, such as untreated Grade 3 psychiatric disorder, Grade 3 disorder not amenable to medical intervention, or any hospitalization within the past 52 weeks that may affect tolerability of study requirements
• History of autoimmune disorders, including but not limited to Crohn's disease, ulcerative colitis, severe psoriasis, and rheumatoid arthritis, that have been exacerbated by previous interferon use
• Any systematic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
• Serious illness including malignancy, active symptomatic coronary artery disease within 24 weeks prior to study entry, or other chronic medical condition that could interfere with safe study completion
• Presence of AIDS-defining opportunistic infections within 12 weeks prior to study entry
• Hemoglobinopathy (e.g., thalassemia major) or any other cause of or tendency to hemolysis. Subjects with thalassemia minor may be enrolled at the discretion of the investigator.
• History of major organ transplantation with an existing functional graft
• Use of antidiabetic medications for any reason within 12 weeks prior to study entry
• Fasting plasma glucose level of at least 126 mg/dl within 42 days prior to study entry or current or previous treatment at any time for diabetes with measures other than diet. Women with a history of gestational diabetes, patients with diabetes or hyperglycemia occurring in the context of short term use of corticosteroids, growth hormone, or other diabetogenic medication, and patients with diabetes or hyperglycemia following an episode of pancreatitis who no longer require treatment for diabetes are not excluded.
• Known osteoporosis
• Known initiation or change in dose of any statins, fibrates, omega-3 fatty acids, bile acid sequestrants, ezetimibe, and niacin derivatives within 12 weeks prior to study entry
• Known allergy, sensitivity, or hypersensitivity to components of the study drugs or their formulation
• Regular and excessive use of alcohol within the 12 weeks prior to study entry. More information on this criterion can be found in the protocol.
• Unwilling to restrict alcohol use during the study to 120 g of alcohol per week or less for men and 60 g of alcohol per week or less for women
• Known glucocorticoid use in supraphysiologic doses (e.g., more than 10 mg per day of prednisone or equivalent doses of other glucocorticoids) within 12 weeks prior to study entry
• Known glucocorticoid use in physiologic replacement doses (e.g., 10 mg or less per day of prednisone or equivalent doses of other glucocorticoids) initiated within 28 days prior to study entry
• History of congestive heart failure corresponding to New York Heart Association Class II or greater
• Current use of prohibited concomitant medications. More information on this criterion is available in the protocol.
• Current participation in experimental studies that include treatments not approved by the FDA or any blinded treatments, with the exception of investigational antiretrovirals available through expanded access programs
• Body mass index (BMI) greater than 40 kg/m2
• Participant or participant's partner is pregnant or breastfeeding