Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- CD4 T cell levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
CD4 T cell levels
时间窗: one year follow up
HIV plasma viral load
时间窗: one year follow up
Clinical HIV infection
时间窗: one year follow up
次要结局
- HIV specific immune responses(One year follow up)
- CD4 specific responses(One year follow up)
- Immune profile(One year follow up)