Efficacy Study of T Cell Vaccination in HIV Infection

NCT ID: NCT00407836

Last Updated: 2009-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2008-11-30

Brief Summary

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

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.

Conditions

HIV Infections

Keywords

HIV; CD4 T cell level; CD4 autoimmunity; Viral load; T cell vaccination; HIV Therapeutic Vaccine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vaccination

One arm of open label T cell vaccination in which all participants will receive the T cell vaccine

Group Type: EXPERIMENTAL

T cell vaccination

Intervention Type: BIOLOGICAL

Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.

T cell vaccination

Intervention Type: BIOLOGICAL

Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection

Interventions

T cell vaccination

Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.

Intervention Type: BIOLOGICAL

T cell vaccination

Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. CD4 cell counts -from 150 to 450/mm3 and stable for at least 12 months, and treatment with HAART for at least 6 months.

2. Positive cell proliferation assay to CD4 molecule

3. Low HIV viral load (<400 - 5000 copies/ml) for at least 12 months

4. No change of antiretroviral treatment for at least 6 months

5. Signed informed consent

Exclusion Criteria

1. Concomitant immunosuppressive or antineoplastic treatment as well as chronic systemic glucocorticoid therapy.

2. Pregnancy and women without any efficacious contraception.

3. Clinically relevant liver disease (AST and/or ALT >2,5x upper limit of normal range, or total bilirubin > 3,5 mg/dl).

4. Serum creatinine >1,8mg/dl or creatinine clearance <30ml/min.

5. Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Soroka University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ben Gurion University of the Negev

Principal Investigators

Klaris Riesenberg, M.D.

Role: STUDY_DIRECTOR

Soroka U Medical Center

Locations

Soroka Medical Center

Beersheba, , Israel

Countries

Israel

References

Abulafia-Lapid R, Bentwich Z, Keren-Zur Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients. J Clin Virol. 2004 Dec;31 Suppl 1:S48-54. doi: 10.1016/j.jcv.2004.09.017.

Reference Type: RESULT

PMID: 15567094 (View on PubMed)

Abulafia-Lapid R, Mayan S, Bentwich Z, Keren-Zur Y, Avbramovitz Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients--an extended open trial. Vaccine. 2005 Mar 18;23(17-18):2149-53. doi: 10.1016/j.vaccine.2005.01.054.

Reference Type: RESULT

PMID: 15755585 (View on PubMed)

Other Identifiers

sor444006ctil

Identifier Type: -

Identifier Source: org_study_id