Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Ultrasensitive RNA Viral load,
研究概览
简要总结
It is becoming clear that a combination of interventions will be desirable to achieve HIV cure. Therefore the investigators propose a pilot proof of concept study, using combination of a number of different interventions for eradicating residual plasma viremia and decreasing HIV reservoirs. The investigators hypothesize that, (i) antiretroviral intensification using Maraviroc, and/or dolutegravir with (ii) Dendritic Cell vaccination using autologous HIV, and (iii) purging intervention using the Class III HDACs, Sirtuin-1, and (iv) decreasing the ratio of long-lived central memory (TCM)/transitional memory (TTM) CD4+ T-cells using Auranofin will provide a synergistic impact leading to a sterilizing cure of HIV infection. Results of this study may provide insightful evidence for planning the next steps using the more efficacious combination of intervention strategies towards HIV sterilizing cure.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •> 18 years old Documented HIV-1 infection.
- •Has voluntarily signed ICF.
- •On HAART ≥ 2 years, without changes in the 24 weeks immediately prior to screening.
- •HIV viral load <50 copies/mL, and never > 50 copies/mL on 2 consecutive occasions in the last 2 years. CD4 count nadir.
- •> 350 cells/ mm3 Current CD4 count > 500 cells/ mm
- •R5 HIV-1 at Screening as defined by proviral DNA genotropism.
排除标准
- •A subject will NOT be eligible for study participation if he/she meets ANY of the following criteria:
- •Any evidence of an active AIDS-defining condition.
- •Any significant acute medical illness in the past 8 weeks.
- •Women who are pregnant or breastfeeding.
- •Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy; investigational agents; immunomodulators (colony-stimulating factors, growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons); coumadin, warfarin, or other Coumadin derivative anticoagulants. Use of an agent definitely or possibly associated with effects on QT intervals: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
- •Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid or nicotinamide within the last 30 days. Potential participants may enroll after a 30-day washout period.
- •Known hypersensitivity to the components of gold salt, nicotinamide or its analogs.
- •Hepatitis B (HBsAg +) or Hepatitis C (HCV RNA +) infection.
- •Known renal insufficiency defined as calculated creatinine clearance (Cockcroft Gault formula) <60 mL/min.
- •Subjects with a laboratory abnormality grade 3 or 4 with the following exceptions: pancreatic amylase, cholesterol, triglyceride, gamma glutamyl transpeptidase, bilirubin.
- •Any condition which, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.
研究组 & 干预措施
ART Intensification Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks
干预措施: Maraviroc (Drug)
ART Intensification Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks
干预措施: Dolutegravir (Drug)
ART Intensification + Nicotinamide Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.
干预措施: Maraviroc (Drug)
ART Intensification + Nicotinamide Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.
干预措施: Dolutegravir (Drug)
ART Intensification + Nicotinamide Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.
干预措施: Sirtuin Histone deacetylase inhibitor (Drug)
ART Intensification + Auranofin Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
干预措施: Maraviroc (Drug)
ART Intensification + Auranofin Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
干预措施: Dolutegravir (Drug)
ART Intensification + Auranofin Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
干预措施: Auranofin (Drug)
ART Intensification + DC vaccine Group
Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.
干预措施: Dolutegravir (Drug)
ART Intensification + DC vaccine Group
Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.
干预措施: Dendritic Cell Vaccine (Biological)
Multi Interventional Group
Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
干预措施: Dolutegravir (Drug)
Multi Interventional Group
Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
干预措施: Dendritic Cell Vaccine (Biological)
Multi Interventional Group
Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
干预措施: Auranofin (Drug)
Multi Interventional Group
Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
干预措施: Sirtuin Histone deacetylase inhibitor (Drug)
结局指标
主要结局
Ultrasensitive RNA Viral load,
时间窗: from baseline and every 4 weeks up to 48 weeks.
Cell-associated HIV RNA
时间窗: from baseline and every 4 weeks up to 48 weeks.
specific HIV antibodies
时间窗: from baseline and every 4 weeks up to 48 weeks
Episomal DNA
时间窗: from baseline and every 4 weeks up to 48 weeks
CD38 and HLA-DR on CD4 and CD8+ cells
时间窗: from baseline and every 4 weeks up to 48 weeks
PBMC for env sequence evolution
时间窗: from baseline and every 4 weeks up to 48 weeks
次要结局
未报告次要终点
研究者
Ricardo Sobhie Diaz, MD, PHD
Associate Professor of Medicine
Federal University of São Paulo