Effect of CCR5 Inhibition by Maraviroc on HIV-1 Infected Subjects Who Require Allogeneic Hematopoietic Cell Transplant for Any Indication and Its Observed Effect on Graft Versus Host Disease and HIV-1 Persistence
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Time to hematopoietic cell and immune recovery
研究概览
简要总结
The goal of this proposal is to determine the effect of maraviroc when it has been a part of the antiretroviral (ART) regimen given immediately after allogeneic hematopoietic cell transplant (allo-HCT) for HIV-1 infected participants who have a hematopoietic malignancy or other underlying disorder requiring an allogeneic transplant. Maraviroc has been given in practice to alleviate symptoms of graft vs. host disease (GvHD). Given its mechanism of action, it may also have an effect on the reservoir size of HIV-1 in infected patients. This study will inform potential future studies, evaluating the effect of this approach on the incidence and severity of GvHD, and determining its effect on HIV-1 reservoir.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
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
- 未提供
排除标准
- •Ongoing AIDS-related opportunistic infection (including oral thrush).
- •Pregnant and/or breastfeeding.
研究组 & 干预措施
Maraviroc after allo-HCT
- Step 1: participants who have received at least 30 days of maraviroc immediately post allo-HCT can be enrolled. Blood will be drawn at 2 time points at least 2 weeks apart, but within 4 weeks, and assessed for HIV-1 reservoir using both DNA assays and cell-associated reactivation by infectivity after stimulation. If any biopsies post allo-HCT are performed as part of standard of care and available, these will also be assessed for HIV-1
- Step 2: If HIV-1 reservoir is undetecable, antiretrovirals (ART) will be stopped in a structured treatment interruption (STI). HIV-1 VLs and CD4+ T-cells check weekly. Week 16, participants will have a large volume blood draw if remain suppressed. If confirmed return of viremia, ART will be reinitiated and he/she will be followed until HIV VL is <50 copies/ml. If he/she remains suppressed at Week 16 and repeat assays confirm no detectable HIV-1, HIV-1 VLs and CD4+ T-cell counts will be checked monthly until Week 52, and then quarterly until Year 5
干预措施: For Step 2: Structured treatment interruption (Other)
Maraviroc after allo-HCT
- Step 1: participants who have received at least 30 days of maraviroc immediately post allo-HCT can be enrolled. Blood will be drawn at 2 time points at least 2 weeks apart, but within 4 weeks, and assessed for HIV-1 reservoir using both DNA assays and cell-associated reactivation by infectivity after stimulation. If any biopsies post allo-HCT are performed as part of standard of care and available, these will also be assessed for HIV-1
- Step 2: If HIV-1 reservoir is undetecable, antiretrovirals (ART) will be stopped in a structured treatment interruption (STI). HIV-1 VLs and CD4+ T-cells check weekly. Week 16, participants will have a large volume blood draw if remain suppressed. If confirmed return of viremia, ART will be reinitiated and he/she will be followed until HIV VL is <50 copies/ml. If he/she remains suppressed at Week 16 and repeat assays confirm no detectable HIV-1, HIV-1 VLs and CD4+ T-cell counts will be checked monthly until Week 52, and then quarterly until Year 5
干预措施: Peripheral blood draw (Procedure)
结局指标
主要结局
Time to hematopoietic cell and immune recovery
时间窗: Up to 100 days after transplant
-In general, the mean time of engraftment of the donor cells is approximately 90 to 100 days post-transplant and this can be monitored by measuring the percent chimerism of donor cells.
Number of participants who experience chimerism
时间窗: At the time of screening
-Chimerism is measured by ≥ 98% of blood cells donor derived
Survival of participants
时间窗: 5 years after transplant
-Number of participants who are alive 5 years after transplant
Event free survival
时间窗: 5 years after transplant
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
HIV-1 proviral DNA levels in peripheral blood
时间窗: Up to week 16 after transplant
* Obtained from peripheral blood * Used to determine if participant can proceed to Step 2
Presence and severity of GvHD
时间窗: Through 5 years after transplant
-GvHD will be measured using the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: IV. Response Criteria Working Group Report
HIV-1 reactivation in stimulated assay
时间窗: Up to week 16 after transplant
* Obtained from peripheral blood * Used to determine if participant can proceed to Step 2
次要结局
- Number of participants who achieve a state of functional cure(Through 5 years after transplant)
- Number of participants who achieve a state of sterilizing cure(Through 5 years after transplant)
- Number of participants who have plasma viral load <50 copies/ml(Through 5 years after transplant)
- Number of participants who have gut immune reconstitution(Through 5 years after transplant)
- Number of participants who have existence of replication competent HIV-1 reservoirs in peripheral blood, gut and other tissue compartments(Through 5 years after transplant)