Biomarkers for Post-treatment Control in HIV: International Multicenter Study of the EU2Cure Research Consortium (EU2Control)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 200
- 主要终点
- Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
研究概览
简要总结
Antiretroviral therapy (ART) has transformed HIV from a deadly disease into a lifelong infection that can be controlled. Nevertheless, in the majority of people living with HIV (PWH), discontinuation of ART results in viral rebound due to a latent proviral reservoir. Rarely, individuals known as post-treatment controllers (PTC) demonstrate prolonged viral control even after ceasing ART. Investigating the underlying mechanisms driving this sustained viral control has been a goal for the HIV research community. However, previous studies have been hindered by the scarcity of PTC cases, thereby restricting the potential for associative and translational research. Consequently, the aim of this study is to collect and meta-analyse the data from prior trials where PTC have been identified, as well as to retrospectively identify PTC from the routine care outside trials in a multicentre, multinational study called EU2Control. The aggregated clinical data, and the already collected material from trials where PWH consented for use in additional studies on HIV, will be analyzed with the goal to identify predictive biomarkers for sustained viral control. This study will be part of the research line on HIV cure from an ongoing collaborative consortium (EU2Cure). The first phase of this research line involves a retrospective cohort for meta-analysis and establishment of a biobank.
详细描述
Baseline demographic and categorical clinical characteristics of PTC and PIC (sex, ART regimen type, early ART initiation) will be summarized as proportions. Continuous variables (age [years], ART duration [years], plasma HIV-1 RNA [copies/mL], leukocyte counts [cells/µL], biochemical parameters) will be summarized separately using descriptive statistics.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PTC: Viremic people living with HIV (HIV-RNA >1000c/mL) before ART initiation. Plasma HIV-RNA off ART ≤400c/mL at least 2 times at ≥24weeks apart and at ≥2/3rds of HIV-RNA measurements. Elite PTC with ≤50c/mL will be identified.
- •Post intervention controller (PIC): People living with HIV from ATI or MAP studies who meet the PTC criteria as per ATI/MAP study defined. Additional stratification occurs according to the duration of and level of suppressed plasma HIV-RNA (e.g. ≤400c/mL off ART at least 2 times for ≥8 weeks apart). This is done to streamline PIC definitions and capture PIC inMAP studies with an ART pause of less than 24 weeks.
- •Controls: non-controllers (NC) with plasma HIV-RNA >1000 c/mL after ART interruption.
- •Suppressors: viremic people living with HIV (HIV-RNA >1000c/mL) before ART initiation who became HIV-RNA <50c/mL suppressed on ART, remained on ART, and never had viral rebound.
排除标准
- •1.Documented refusal of data use for research
结局指标
主要结局
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
时间窗: 1 year
Reservoir size will be measured as intact proviral HIV DNA and reported as log copies per 10\^6 CD4+ cells. Reservoir size in PTC, PIC, and NC before and after ATI will be described according to data distribution.
Total integrated HIV DNA reservoir size in PTC and PIC before and during ATI
时间窗: 1 year
Reservoir size will be measured as total integrated HIV DNA and reported as log copies per 10\^6 PBMC. Reservoir size in PTC, PIC, and NC before and after ATI will be described according to data distribution.
Inducible HIV reservoir size in PTC and PIC before and during ATI
时间窗: 1 year
Reservoir size will be measured as inducible HIV and reported as log HIV RNA or HIV DNA copies. Reservoir size in PTC, PIC, and NC before and after ATI will be described according to data distribution.
Time from the start of ATI until first measurement of HIV RNA >50 copies/mL in PTC and PIC.
时间窗: 1 year
A survival analysis will be done for all PTC, PIC and NC who have been sourced from ATI trials. Baseline will be set as the start of the treatment interruption. Time will be noted in weeks until first measurement of HIV-RNA \>50 copies/mL for all study participants. Levels correspond to elite controller definition (Deeks \& Walker, 2007), PTC definition, and level below which HIV onward transmission rarely occurs (Gray et al., 2001). Analysis is by Kaplan Meier and Cox Proportional Hazard models with loss of viral control as event. Independent variables can be timing of ART initiation, duration of ART, HIV cure intervention (if any), demographic parameters (sex, age, place of birth, country of residence), viral dynamics (subtype, reservoir size) and immune characteristics (cd4+ count, cd8+ count, cd4/cd8 ratio).
Time from the start of ATI until first measurement of HIV RNA >400 copies/mL in PTC and PIC.
时间窗: 1 year
A survival analysis will be done for all PTC, PIC and NC who have been sourced from ATI trials. Baseline will be set as the start of the treatment interruption. Time will be noted in weeks until first measurement of HIV-RNA \>400 copies/mL for all study participants. Levels correspond to elite controller definition (Deeks \& Walker, 2007), PTC definition, and level below which HIV onward transmission rarely occurs (Gray et al., 2001). Analysis is by Kaplan Meier and Cox Proportional Hazard models with loss of viral control as event. Independent variables can be timing of ART initiation, duration of ART, HIV cure intervention (if any), demographic parameters (sex, age, place of birth, country of residence), viral dynamics (subtype, reservoir size) and immune characteristics (cd4+ count, cd8+ count, cd4/cd8 ratio).
Time from the start of ATI until first measurement of HIV RNA > 1000 copies/mL in PTC and PIC.
时间窗: 1 year
A survival analysis will be done for all PTC, PIC and NC who have been sourced from ATI trials. Baseline will be set as the start of the treatment interruption. Time will be noted in weeks until first measurement of HIV-RNA \>1000 copies/mL for all study participants. Levels correspond to elite controller definition (Deeks \& Walker, 2007), PTC definition, and level below which HIV onward transmission rarely occurs (Gray et al., 2001). Analysis is by Kaplan Meier and Cox Proportional Hazard models with loss of viral control as event. Independent variables can be timing of ART initiation, duration of ART, HIV cure intervention (if any), demographic parameters (sex, age, place of birth, country of residence), viral dynamics (subtype, reservoir size) and immune characteristics (cd4+ count, cd8+ count, cd4/cd8 ratio).
Number and severity of adverse events during and after ATI.
时间窗: 1 year
Medical events in PTC, PIC and NC recorded in the clinical file will be described using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. If medical events have been reported using varied terminology in the ATI trials, two separate evaluators will reclassify them using CTCAE v5.0 terminology. In instances of conflicting classifications, an impartial researcher will make the final determination.
Biobank with samples from PTC, PIC and NC including sampling time points and material available.
时间窗: 1 year from screening
Available samples will be indexed from previously performed ATI trials. An inventory will be made of the number of samples, type, volume, time of sampling, sampling technique and storage medium.
次要结局
未报告次要终点
研究者
Casper Rokx
Ass. Prof. Dr.
Erasmus Medical Center