Therapy to Elevate CD4 Counts in HIV-1 Disease

Study Overview
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Brief Summary
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For more than 20 years, alpha-1-proteinase inhibitor therapy has been the standard treatment for patients who have inherited alpha-1-proteinase inhibitor deficiency. Adult patients with this condition eventually develop emphysema. Most HIV-1 patients who have low viral load also have alpha-1-proteinase inhibitor deficiency. The number of CD4 cells in blood increases when alpha-1-proteinase inhibitor increases. Patients will be asked to participate in a pilot study to see whether the use of Zemaira® (alpha-1-proteinase inhibitor) can increase blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts.

Detailed Description
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HIV-1 patients will be asked to participate in a pilot study to see whether the use of Zemaira increases blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts. HIV-1 patients will receive weekly treatment with Zemaira for 8 weeks by intravenous infusion. Blood will be collected immediately prior to each infusion. Blood will be collected at each visit. Exploratory assessments and not pre-specified outcome measurements will include complete blood count, lymphocyte phenotype, HIV-1 viral load, lipid levels, blood chemistry, and markers of inflammation from patient medical records. Exploratory and not pre-specified outcome measures will include extended lymphocyte phenotype and lymphocyte function using residual blood collected.

Official Title
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Zemaira (Alpha-1-Proteinase Inhibitor) Therapy in HIV-1 Disease

Conditions
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HIV Disease

Intervention / Treatment
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* Biological: alpha-1-Proteinase Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 patients must have confirmed HIV-1 disease, diagnosed using the standard criteria and be on antiretroviral therapy. Patients with inherited alpha-1 proteinase inhibitor deficiency (PIzz) must not have previously received alpha-1 proteinase inhibitor therapy. Uninfected volunteers will be age and gender matched. HIV-1 patients must have measurable disease, defined as HIV-1 infected patients on antiretroviral therapy with undetectable HIV RNA (<500 HIV-1 RNA copies/ml) and CD4 counts more than 200 and less than 400 cells/uL. Age at least 18 years and under 65 years. HIV-1 patients must have active alpha-1 proteinase inhibitor below 11uM (normal is 18-53 uM). HIV-1 patients must have one year history (prior to the study) with CD4 counts greater than 200 and less than 400 cells/uL. Volunteers must have no evidence of malignancy. Exclusion Criteria: Recent illness that will prevent the patient from participating in required study activities. Patients receiving other investigational agents. Patients with known malignancies. Patients with more than 500 HIV RNA copies/mL. Patients with more than 400 CD4 cells/uL. Uncontrolled illness including, but not limited to, ongoing or active infection, myeloid dysplastic syndrome, anemia, bone marrow failure, DiGeorge Syndrome, thymic disorders, or psychiatric illness/social situations that would limit compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alpha-1 proteinase inhibitor in HIV<br>HIV-1 infected individuals treated with Alpha-1 proteinase inhibitor | Biological: alpha-1-Proteinase Inhibitor<br>* Alpha-1-Proteinase Inhibitor was delivered I.V. A patient weighing 150 pounds was infused with approximately ½ cup containing 8.4 grams of alpha-1-Proteinase Inhibitor. Patients were admitted to hospital for infusion. The I.V. infusion was approximately 1 teaspoon/minute. Patients received weekly infusions of alpha-1-Proteinase Inhibitor for 8-12 weeks. At the time of infusion, 40ml (3 Tablespoons) of blood was collected (IRB approval #R04-003). The blood sample was used to monitor viral load, CD4 cell numbers, and alpha-1-Proteinase Inhibitor.<br>* Other names: Prolastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4/CD8 Ratio |  | 9 weeks after initiation of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD4 counts, cholesterol