Active Immunotherapy Against HIV During Highly Active Anti-retroviral Therapy Followed by Repeated Treatment Interruptions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Safety and feasibility
研究概览
简要总结
In this study, the investigators evaluated a therapeutic HIV-1 DNA vaccine administered with a novel topical application method to 12 chronically HIV-infected cART treated patients. The HIV DNA plasmids used in this study encode for envelope gp160 of HIV-1 subtypes A, B and C, rev B, Gag A and B and reverse transcriptase (RT) B. The patients were randomly assigned to three groups; group 1 (n=4) were immunized six times with 0.4 mg of HIV DNA plasmids topically, group 2 (n=4) were immunized six times with 0.4 mg of HIV DNA plasmids topically and treated with 500 mg of hydroxyurea daily until visit 10, group 3 (n=4) four patients received placebo. The immunization was performed during three cycles of 7 weeks of cART followed by four weeks of therapy interruption. After the last cycle of cART the patients were maintained on a definitive treatment interruption until CD4+ T cell counts dropped below 350/ mm3 at two time points. Cellular and humoral immune responses, viral load and CD4+ T a cell count was analysed throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Aged between 18 and 60 years
- •Female, who is documented infertile or in menopause since at least 1 year, or male, who are willing not father a child for the duration of the study.
- •HIV infection detected by two serological and/or HIV plasma RNA tests
- •On HAART for at least 6 months with less than 50 copies/ml of plasma HIV-1 RNA at two determinations over 3 months
- •Current CD4 count above 400
- •CD4 count nadir >200
- •Viral isolate pre ART available is preferable but not mandatory
- •Willing to consider stopping HAART repeatedly.
- •Willing to conform to a low alcohol intake (maximum of one glass per day)
- •Able to tolerate didanosine and hydroxyurea
- •Willing to change their HAART to exclude NNRTI and stavudine
- •Able to give informed consent
- •Availability for follow-up for planned duration of the study
排除标准
- •Patients with ongoing infection(s) other than HIV.
- •Prior or current pancreatitis or history of alcohol abuse.
- •Ongoing neuropathy and history of more than grade 1 neuropathy.
- •History of mutations to more than one class of anti-retroviral drugs or switched drugs more than once due to failure.
- •Sun or solarium exposure at the immunizing sites one month before or during the trial.
- •Cortisone treatment, systemic or local at the immunizing sites, one month before or during the trial.
- •Patients with signs of autoimmune diseases
- •Patients with creatinine > 2mg/dl, Hb < 12g/dl, leukocytes < 3,000ul, platelets <150,000/ul and LFT > 5x upper limit of normal
- •Patients on any immune modulating or investigational drug
- •Anamnestic allergy to kanamycin, plasmid gene products
结局指标
主要结局
Safety and feasibility
The safety and feasibility of dermal HIV-1 DNA vaccination will be evaluated by recording all medical events. They will be graded as to their seriousness, severity and relationship to the immunization. Plasma HIV-1 RNA levels and T-cell levels will be closely monitored. In addition to this the patient's individual experience and quality of life will be assessed.
次要结局
- Treatment effects