Efficacy Study of T Cell Vaccination in HIV Infection

Study Overview
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Brief Summary
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The hallmark of HIV infection and AIDS is the continuous attrition of CD4 T cells. One of the mechanisms that may account for the CD4 attrition , is autoimmunity against the CD4 T cells, caused by autologous immune cells. Vaccination against autoimmune reactive T cells has been successfully tried in animal models of autoimmune diseases and is now being tried in patients with Multiple Sclerosis. The purpose of the present study is to test this hypothesis in HIV infection. We will vaccinate HIV infected patients in whom specific autoimmune reactivity against CD4 is present , with their own CD4 reactive T cells. Following that, we shall study the patients and find out if the T cell vaccination caused a rise in CD4 T cell levels, and whether it influenced HIV viral load, as well as HIV and CD4 specific immunity.

Detailed Description
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The study will be based on forty HIV infected patients, receiving anti retroviral treatment (HAART), with CD4 levels between 150-350 and HIV plasma viral load < 5000, for at least 12 months and despite continuous anti-retroviral treatment. The patients will be randomly divided into two groups, one that will get the T cell vaccination, and the other that will serve as controls. The T cell vaccine will be prepared from autologous T cells that responded by specific proliferation to recombinant CD4, further expanded in vitro by IL-2, and then fixed by glutaraldehyde. Each vaccine portion will consist of 10,000 such cells suspended in saline and given subcutaneously every three months during the first year of the trial. The outcome measures will be CD4 levels, specific immunity to HIV antigens, immune activation profile and HIV plasma viral loads, determined sequentially during the 24 months of the trial. These outcome measures will be compared between the experimental and the control groups, to determine if this mode of treatment is effective in influencing CD4 levels as an additional mode of treatment during HIV infection.

Official Title
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Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: T cell vaccination
* Biological: T cell vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD4 cell counts -from 150 to 450/mm3 and stable for at least 12 months, and treatment with HAART for at least 6 months. Positive cell proliferation assay to CD4 molecule Low HIV viral load (<400 - 5000 copies/ml) for at least 12 months No change of antiretroviral treatment for at least 6 months Signed informed consent Exclusion Criteria: Concomitant immunosuppressive or antineoplastic treatment as well as chronic systemic glucocorticoid therapy. Pregnancy and women without any efficacious contraception. Clinically relevant liver disease (AST and/or ALT >2,5x upper limit of normal range, or total bilirubin > 3,5 mg/dl). Serum creatinine >1,8mg/dl or creatinine clearance <30ml/min. Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccination<br>One arm of open label T cell vaccination in which all participants will receive the T cell vaccine | Biological: T cell vaccination<br>* Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.<br>Biological: T cell vaccination<br>* Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 T cell levels |  | one year follow up | 
| HIV plasma viral load |  | one year follow up | 
| Clinical HIV infection |  | one year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV specific immune responses |  | One year follow up | 
| CD4 specific responses |  | One year follow up | 
| Immune profile |  | One year follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, CD4 T cell level, CD4 autoimmunity, Viral load, T cell vaccination, HIV Therapeutic Vaccine