Immune Therapy and Analytical Treatment Interruption in HIV+ Participants Who Received an Allogeneic Stem Cell Transplantation (ITATI)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 4
- 主要终点
- Time to reappearance of HIV-1 total reservoir
研究概览
简要总结
The availability of antiretroviral therapy (cART) for HIV-1 infection has led to a reduction in morbidity in patients with chronic HIV infection. However, cART does not eliminate HIV-1 that persists as a latent infection in cellular reservoirs. Usually, HIV viremia rapidly rebounds if antiretroviral therapy is interrupted. Consequently, HIV infected individuals must commit to expensive, life-long therapies and must tackle problems associated with chronic infection and uninterrupted cART, including continuous clinical and laboratory monitoring, drug toxicities, and chronic immune activation/inflammation.
Currently, there is an emerging interest in developing safe and affordable curative strategies that would eliminate the need for lifelong therapy. However, to date only allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown results in decreasing the HIV-1 reservoirs.
The IciStem Consortium (www.icistem.org) has assembled the largest and most exhaustive observational cohort for the study of HIV reservoir dynamics in allo-HSCT HIV+ individuals with severe hematological malignancies worldwide. Within the cohort, only individuals transplanted with a donor with thw CCR5A32 mutation have shown signs of HIV remission. On the other side broadly neutralizing antibodies (bNAbs) have shown the potential to control HIV infection. This study intends to evaluate if the allo-HSCT combined with the additional application of bNAbs is effective to control HIV replication.
详细描述
The availability of antiretroviral therapy (cART) for HIV-1 infection has led to a reduction in morbidity in patients with chronic HIV infection. However, cART does not eliminate HIV-1 that persists as a latent infection in cellular reservoirs. Usually, HIV viremia rapidly rebounds if antiretroviral therapy is interrupted. Consequently, HIV infected individuals must commit to expensive, life-long therapies and must tackle problems associated with chronic infection and uninterrupted cART, including continuous clinical and laboratory monitoring, drug toxicities, and chronic immune activation/inflammation.
Currently, there is an emerging interest in developing safe and affordable curative strategies that would eliminate the need for lifelong therapy. However, to date only allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown results in decreasing the HIV-1 reservoirs.
The IciStem Consortium (www.icistem.org) has assembled the largest and most exhaustive observational cohort for the study of HIV reservoir dynamics in allo-HSCT HIV+ individuals with severe hematological malignancies worldwide. Within the cohort, only individuals transplanted with a donor with thw CCR5A32 mutation have shown signs of HIV remission. On the other side broadly neutralizing antibodies (bNAbs) have shown the potential to control HIV infection. This study intends to evaluate if the allo-HSCT combined with the additional application of bNAbs is effective to control HIV replication.
Detailed Description:
The implementation of highly effective, convenient, and well-tolerated combination antiretroviral therapy (cART) for HIV-1 infection has substantially reduced AIDS-related morbidity and mortality. However, cART does not eliminate HIV-1 that persists as a latent infection in cellular reservoirs, including resting memory CD4+ T cells, leading to an underlying raised state of immune activation and subsequent immune senescence. Of note, HIV viremia rapidly rebounds if antiretroviral therapy is interrupted. Consequently, HIV infected individuals must commit to expensive, life-long therapies and must tackle problems associated with chronic infection and uninterrupted cART, including continuous clinical and laboratory monitoring, drug toxicities, and chronic immune activation/inflammation. Therefore, there is an emerging interest in developing safe and affordable curative strategies that would eliminate the need for lifelong therapy while improving the health of infected subjects and reducing the risk of viral transmission to uninfected individuals. So far, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only intervention to date that systematically reduces HIV-1 reservoirs to undetectable levels regardless of the CCR5Δ32 donor status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •More than 2 years post-HSCT
- •Being off immunosuppression for at least one year (related to allo-HSCT)
- •Undetectable levels of HIV replication competent reservoirs in blood (< 0,1 IUPM).
- •CD4 count levels higher than 200 cel/mm
- •Aged at least 18 years and not older than 65 at the day of screening
- •Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
- •In the opinion of the principal investigator or designee, the participant has understood the information provided and capable of giving written informed consent.
- •If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner1) from 14 days prior to the first bNAbs administration until at least 6 months after the last bNAbs administration; all female volunteers must be willing to undergo urine pregnancy tests at time points specified.
- •If heterosexually active male; willing to use an effective method of contraception (anatomical sterility in self) or agree on the use of an effective method of contraception by his partner(hormonal contraception, intra-uterine device (IUD), or anatomical sterility1 from the day of the first bNAbs administration until 6 months after the last bNAbs administration.
- •Willing to accept blood draws at time points specified.
- •Not sharing injection drug equipment, such as needles.
- •Condom use nor diaphragm are considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.
排除标准
- •Pregnancy or lactating
- •Participation in another clinical trial within 12 weeks of study entry (at screening period).
- •History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.
研究组 & 干预措施
Experimental group
The participant will perform an Analytical Treatment Interruption (ATI) of up to 18 months of duration, and during the first 8 months, a temporary immune intervention including the combination of the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074, which will be infused once per month.
干预措施: Analytical Treatment Interruption + bNAbs infusion (Drug)
结局指标
主要结局
Time to reappearance of HIV-1 total reservoir
时间窗: From Baseline to 18 months
Time to reappearance of HIV-1 total reservoir (determined by the number HIV-DNA copies per 106 CD4+ T cells using ddPCR) after ART interruption.
Time to reappearance of HIV-1 replication competent reservoir
时间窗: From Baseline to 18 months
Time to reappearance of HIV-1 replication competent reservoir (determined by the number of infectious units per 106 CD4+ T cells (IUPM) using a viral outgrowth assay) after ART interruption.
Time to reappearance of HIV-1 viremia
时间窗: From Baseline to 18 months
Time to reappearance of HIV-1 viremia (plasma HIV-1 RNA level \> 50 copies/ml in 2 consecutive measurements) after ART interruption.
次要结局
- Rate and severity of adverse events (AE) and serious adverse events (SAE)(From Baseline to 18 months)
- Serum levels of 3BNC117 and 10-1074(From Baseline to 18 months)