HIV Infections Clinical Research Study

What is the purpose of this study?

Insulin resistance is common in people coinfected with HIV and Hepatitis C virus (HCV) and is associated with poor responses to treatment for HCV. Pioglitazone is an FDA-approved medication for the treatment of type 2 diabetes. It works by increasing the body's sensitivity to insulin. The purpose of this study is to determine whether treatment with pioglitazone prior to HCV treatment with peginterferon and ribavirin is safe and effective in improving the treatment outcome in insulin-resistant, HIV/HCV-coinfected people for whom previous treatment with peginterferon and ribavirin was unsuccessful.

Can I participate in this study?

You may be eligible for this study if you meet the following criteria:

• Conditions: HIV Infections, Hepatitis C
• Age: Between 18 - 100 Years
• Gender: Male or Female
• +

  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 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 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 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:

  Detectable HCV RNA 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 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 or any other cause of or tendency to hemolysis

  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 or receipt of treatment for osteopenia or osteoporosis within 12

  weeks prior to study entry with the following medications: risedronate ibandronate

  etidronate raloxifene teriparadate aledronate or calcitonin.

  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 35 kg/m2

  Participant or participant's partner is pregnant or breastfeeding

Detail Study Description

New and better strategies for the treatment of HCV in HIV/HCV-coinfected people are urgently needed. Standard therapy for HCV includes treatment with peginterferon plus ribavirin. Peginterferon is a modified form of the drug interferon and is used either alone or in combination with ribavirin for the treatment of HCV. Ribavirin works by stopping HCV from multiplying inside the body. Sustained virologic response rates in past large studies of peginterferon plus ribavirin used for treating HCV types 1 or 4 ranged from 11% to 29%. Studies have shown that insulin resistance in HCV-infected people who are HIV uninfected leads to poorer HCV treatment response. Improving the body's response to insulin may also improve the outcome of treatment for HCV. Participants in this study will take pioglitazone for up to 28 weeks. At Weeks 2, 4, 8, 12, and 18, participants will receive clinical assessments. At Week 24, participants will undergo additional tests to ensure that they can enter Step 2 of the study. Participants who are able to continue will then take peginterferon and ribavirin in addition to the pioglitazone for another 48 weeks. Clinical assessments will take place at the time of entry and Weeks 2, 4, 8, 12, 16, and 24 of Step 2. Participants who do not exhibit a response to the treatment at Weeks 12 or 24 will not continue Step 2, as it is unlikely that further treatment will elicit a response. Participants who continue in the study will return to the study site for assessments at Weeks 32, 40, and 48. Participants who have not responded to treatment by Week 48 will no longer receive any of the study drugs. Follow-up visits will be held at Weeks 60 and 72. The assessments done at clinic visits may include any or all of the following tests: thyroid function, hematology and chemistry, fasting plasma glucose, liver function, gamma-glutamyl transferase, pregnancy, CD4/CD8, HIV, qualitative HCV RNA, quantitative HCV RNA, HCV genotyping, and HCV virologic response.

Study Treatments

Pioglitazone, Peginterferon, Ribavirin

Last Updated: February 2010