Clinical trial NCT00407836: Efficacy Study of T Cell Vaccination in HIV Infection
Official title: Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
CD4 T cell level
CD4 autoimmunity
Viral load
T cell vaccination
HIV Therapeutic Vaccine
Lead sponsor: Soroka University Medical Center
Sponsor class: OTHER
First posted: 2006-12-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: CD4 T cell levels
timeFrame: one year follow up
measure: HIV plasma viral load
timeFrame: one year follow up
measure: Clinical HIV infection
timeFrame: one year follow up
Secondary outcomes:
measure: HIV specific immune responses
timeFrame: One year follow up
measure: CD4 specific responses
timeFrame: One year follow up
measure: Immune profile
timeFrame: One year follow up
Other outcomes:
Locations:
city: Beer Sheba
country: Israel
facility: Soroka Medical Center
Study officials:
affiliation: Soroka U Medical Center
name: Klaris Riesenberg, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.