HIV Disease
Conditions
Keywords
CD4 counts, cholesterol
Brief summary
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
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.
Interventions
BIOLOGICALalpha-1-Proteinase Inhibitor
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.
Sponsors
CSL Behring
Institute for Human Genetics and Biochemistry
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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. 2. 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. 3. Age at least 18 years and under 65 years. 4. HIV-1 patients must have active alpha-1 proteinase inhibitor below 11uM (normal is 18-53 uM). 5. HIV-1 patients must have one year history (prior to the study) with CD4 counts greater than 200 and less than 400 cells/uL. 6. Volunteers must have no evidence of malignancy.
Exclusion criteria
1. Recent illness that will prevent the patient from participating in required study activities. 2. Patients receiving other investigational agents. 3. Patients with known malignancies. 4. Patients with more than 500 HIV RNA copies/mL. 5. Patients with more than 400 CD4 cells/uL. 6. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CD4/CD8 Ratio | 9 weeks after initiation of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alpha-1-Proteinase Inhibitor in HIV This pilot study was performed to examine the efficacy of alpha-1 proteinase inhibitor augmentation in 4 HIV-1 infected patients undergoing research treatment to elevate alpha-1-proteinase inhibitor and thereby, CD4 helper immune cells.Study subjects were evaluated at Baseline and weekly for at least 8 weeks. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet criteria for analysis | 1 |
Baseline characteristics
| Characteristic | Alpha-1-Proteinase Inhibitor in HIV |
|---|---|
| active alpha-1 proteinase inhibitor | 8 μM STANDARD_DEVIATION 3 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| CD4/CD8 Ratio | 0.40 Ratio STANDARD_DEVIATION 0.19 |
| CD4 counts | 294 cells/uL STANDARD_DEVIATION 125 |
| CD8 | 829 cells/uL STANDARD_DEVIATION 281 |
| Region of Enrollment United States | 4 participants |
| Sex/Gender, Customized Female | 0 participants |
| Sex/Gender, Customized Male | 4 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
CD4/CD8 Ratio
Time frame: 9 weeks after initiation of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alpha-1-Proteinase Inhibitor in HIV | CD4/CD8 Ratio | 0.44 Ratio | Standard Deviation 0.3 |