Clinical trial NCT01370018: Therapy to Elevate CD4 Counts in HIV-1 Disease
Official title: Zemaira (Alpha-1-Proteinase Inhibitor) Therapy in HIV-1 Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Disease
Keywords: CD4 counts
cholesterol
Lead sponsor: Institute for Human Genetics and Biochemistry
Sponsor class: OTHER
Collaborators: name: CSL Behring
First posted: 2011-06-09
Enrollment: 4
Sex: MALE
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: CD4/CD8 Ratio
timeFrame: 9 weeks after initiation of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Cabrini Medical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Cynthia L Bristow, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Medical Center
name: Jose Cortes, MD
role: STUDY_DIRECTOR
References:
citation: Bristow, C.L., Cortes, J., Mukhtarzad R., Trucy, M., Franklin, A., Romberg, V., Winston, R. 2010. α1Antitrypsin therapy increases CD4+ lymphocytes to normal values in HIV-1 patients. In Soluble Factors Mediating Innate Immune Responses to HIV Infection, (ed. M. Alfano). Bentham Science Publishers, http://www.alpha1biologics.com/BristowChapter.pdf
citation: Bristow CL, Modarresi R, Babayeva MA, LaBrunda M, Mukhtarzad R, Trucy M, Franklin A, Reeves RE, Long A, Mullen MP, Cortes J, Winston R. A feedback regulatory pathway between LDL and alpha-1 proteinase inhibitor in chronic inflammation and infection. Discov Med. 2013 Nov;16(89):201-18.
citation: Bristow CL, Ferrando-Martinez S, Ruiz-Mateos E, Leal M, Winston R. Development of Immature CD4+CD8+T Cells Into Mature CD4+ T Cells Requires Alpha-1 Antitrypsin as Observed by Treatment in HIV-1 Infected and Uninfected Controls. Front Cell Dev Biol. 2019 Nov 21;7:278. doi: 10.3389/fcell.2019.00278. eCollection 2019.