Cohort Study to Understand Resistance and HIV Eradication (CURE): Observational Studies of Antiretroviral Drug Treatment Success and Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 1
- 主要终点
- Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency
研究概览
简要总结
The purpose of this observational study is to characterize which immune system cells hide the latent reservoir of HIV by counting the number of latent HIV in different subsets of CD4 cells. Observations will also be made on other possible mechanisms of HIV persistence by looking at cellular factors such as APOBEC3 and drug transporters. The purpose of this study is to develop new strategies to reduce and possibly eliminate the latent reservoir in HIV infected adults.
详细描述
Memory CD4 cells may provide a reservoir of latent HIV that cannot be completely eliminated using currently available anti-HIV medications. The overall goal of this observational study is to develop new strategies to eliminate the latent HIV reservoir in HIV infected individuals. CD4-cell subsets, cellular anti-HIV factors, and cellular drug transporters will be observed to determine which resting memory cells hide latent HIV and to determine the mechanisms responsible for the persistence of the latent HIV reservoir.
This study will last for at least 3 years. The screening visit will include medical history, contact information, urine collection, and a physical exam. Participants will be assigned to one of five groups:
- Group 1 will consist of intensively studied adults initiating potentially suppressive drug therapy. At the screening visit, Group 1 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
- Group 2 will consist of intensively studied, well-suppressed adults on highly active antiretroviral therapy (HAART). At the screening visit, Group 2 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
- Group 3 will consist of nonintensively studied adults initiating potentially suppressive drug therapy. Group 3 participants will undergo blood draws at all visits.
- Group 4 will consist of nonintensively studied, well-suppressed adults on HAART. Group 4 participants will undergo blood draws at all visits.
- Group 5 will consist of participants who are currently in the Merck Expanded Access Program receiving raltegravir. At the screening visit, Group 5 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
For all participants undergoing blood draws only, visits will occur every 3 months for about 3 years. For patients undergoing leukapheresis, visits will occur every 6 months for about 3 years. At each visit, blood collection, documentation of current HAART, and updating of contact information will occur. Participants are encouraged to provide additional blood samples to be stored at all visits.
Participants in Groups 1, 2, or 5 may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing completely from the study. If specimens are not obtained for any reason at any visit, participants in Groups 1, 2, or 5 will default to either Group 3 or Group 4. Antiretroviral medications will not be provided by this study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- 未提供
排除标准
- •Viral load "blip" greater than 2,000 copies/ml during current suppressive regimen
- •Consistent low level viral load (between 50 and 2,000 copies/ml) during current regimen
- •Change in currently suppressing HAART before study entry
- •Self-reported or clinician-reported nonadherence to earlier antiretroviral regimens
- •Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
- •Weight less than 110 lbs
- •Blood transfusion within the 6 months prior to study entry
- •Platelets less than 50 cells/mm3
- •INR greater than 2.0 if participants are on warfarin
- •Heart disease with recent angina or MI within 1 year prior to study entry
- •Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less
- •Prior ART that included only one or two drugs
- •Pregnancy
- •Inclusion Criteria for Group 5:
- •HIV infected
- •Currently taking or about to begin raltegravir with optimized background HAART
- •Exclusion Criteria:
- •Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
- •Weight less than 110 lbs
- •Blood transfusion 6 months prior to study entry
- •Platelets less than 50/mm3
- •INR greater than 2.0 if participants are on warfarin
- •Heart disease with recent angina or MI within 1 year prior to study entry
- •• Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less
- •Pregnancy
结局指标
主要结局
Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency
时间窗: At the end of the study
次要结局
- Characterization of the effects of immune activation on the latent reservoir of HIV(At the end of the study)
- Determination of the role of drug transporters in chemotherapeutically suppressed patients(At the end of the study)
- Determination of the association of protein regulation with cellular toxicity and the latent HIV reservoir in chemotherapeutically suppressed participants(At the end of the study)
- Characterization of memory CD4 cell subsets isolated from chemotherapeutically suppressed participants(At the end of the study)
- Evidence of HIV evolution(At the end of the study)
- Quantification of the amount of latent HIV in each memory cell type in chemotherapeutically suppressed participants(At the end of the study)
- Characterization of certain proteins in memory CD4-cell subsets in chemotherapeutically suppressed participants(At the end of the study)
研究者
Richard T D'Aquila
Professor of Medicine, Vanderbilt University
National Institute of Allergy and Infectious Diseases (NIAID)