A Phase IIA Randomized Double-blind Placebo-controlled Single-centre Study of the Effect of Bacillus Calmette-Guérin (BCG) Vaccination on the HIV Latent Reservoir
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change in size of the HIV-1 latent reservoir at 6 months
研究概览
简要总结
A phase IIA randomized double-blind placebo-controlled single-centre study of the effect of Bacillus Calmette-Guérin (BCG) vaccination on the HIV latent reservoir
详细描述
Background and Rationale:
HIV infection affects around 40 million people globally and is incurable due to persistence of viral genetic material within the host genome as the latent reservoir. Patients within the Swiss HIV Cohort Study with latent tuberculosis were recently shown to have a reduced set point HIV viral load compared to tuberculosis (TB)-naïve individuals. The BCG vaccine has been shown to have wide-ranging immunostimulatory effects and can simulate latent tuberculosis infection.
Objective(s):
The purpose of this study is to characterise potential sustained and clinically relevant effects of the BCG vaccine on the size of the latent HIV-1 reservoir in individuals with stable treated HIV-1 infection with suppressed viremia.
The study seeks primarily to determine the effect of a single dose of the BCG vaccine on the size of the latent HIV-1 viral reservoir over a period of up to 6 months post-administration compared to the size at baseline.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent as documented by signature (see Informed Consent Form),
- •Age ≥18 years,
- •HIV-1 infection under continuous antiretroviral therapy for ≥1.5 years as requested in the Systems X Cohort,
- •Current participation in the Swiss HIV Cohort Study and past participation in the Systems X Cohort.
排除标准
- •History of virological failure or treatment interruption at any time, defined as HIV-1 viral load >200c/ml at two consecutive measurements at least 4 weeks apart,
- •CD4 T-cell count <200/μl at any time or <350/μl during the past 1 year
- •Presence of other relevant immunosuppression according to the investigator in addition to HIV (a daily steroid intake of ≥20mg is considered clinically relevant),
- •History of or current clinical evidence of active tuberculosis,
- •Previous positive tuberculin skin test or tuberculosis INF-gamma release assay (Quantiferon-Test) within the past 10 years,
- •Previous BCG-vaccination within the past 10 years,
- •Known allergy to BCG vaccine or any of its components,
- •Documented current febrile illness at screening or in the past 7 days.
- •Women who are pregnant or breast-feeding
研究组 & 干预措施
Early Group
We will conduct a randomized, double-blind trial using a stepped-wedge design and involving a total of 60 patients with stable treated HIV and suppressed viral load who will all receive the BCG vaccine during the course of the study. Patients will be divided into two groups of equal size (early and late groups regarding administration of the BCG verum). The trial will be placebo-controlled and double-blind. Patients in the early group will receive the BCG verum at the beginning of Treatment Phase 1, and then the placebo at the beginning of Treatment Phase 2.
干预措施: BCG Vaccine AJVaccines (Biological)
Late Group
Patients in the late group will receive placebo at the beginning of Treatment Phase 1 and then the BCG verum at the beginning of Treatment Phase 2.
干预措施: BCG Vaccine AJVaccines (Biological)
结局指标
主要结局
Change in size of the HIV-1 latent reservoir at 6 months
时间窗: 6 months for each patient
The primary outcome will be the change in size of the HIV-1 latent reservoir at 6 months post-BCG vaccination compared to pre-vaccination in all patients, with each patient serving as their own control. This HIV-1 latent reservoir size will be measured as total HIV-1 DNA in peripheral blood mononuclear cells, a well-established and extensively validated marker for the HIV-1 reservoir found to be sensitive, clinically relevant and feasible in larger populations.
次要结局
- The change in size of the HIV-1 latent reservoir at 3 months(3 months for each patient)
- The frequency and incidence of adverse events of interest in the verum group compared to the placebo group(9 months)
- The change in size of the HIV-1 latent reservoir at 3 months (in all patients) and 9 months (in the early group) post-BCG vaccination compared to pre-vaccination(9 months for each patient)