Biomarkers for Post-treatment Control in HIV: International Study of the EU2Cure Research Consortium (Phase I) (EU2Control)
2026年7月7日 更新者：Casper Rokx、Erasmus Medical Center
Biomarkers for Post-treatment Control in HIV: International Multicenter Study of the EU2Cure Research Consortium (EU2Control)
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.
調査の概要
詳細な説明
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.
研究の種類
観察的
入学 (推定)
200
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Casper Rokx
- 電話番号：+31618069137
- メール：c.rokx@erasmusmc.nl
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
はい
サンプリング方法
確率サンプル
調査対象母集団
People living with HIV meeting PTC inclusion criteria from previous ATI trials.
In addition, PTC from routine care will be identified and included.
Non controllers will be identified from ATI trials and routine care.
To analyse the reservoir size, PTC (both from routine care and ATI trials) will be matched in a 1:1 ratio with non-controllers (NC).
We will also match NC to a control group of people living with HIV who did not undergo an ATI (Suppressors).
Matching will be performed on gender, age at the start of ATI (+/- 5 years, or age of first included sampling if no ATI performed), current CD4+ (+/- 25%, at the start of ATI or first included sampling if no ATI performed) and total years on ART if possible (+/-1 year, if <5 years on ART.
If >5 years on ART: +/- 2 years), if possible.
When matching on all criteria is impossible, in order of priority, matching will be done on total years on ART, gender, CD4 T-cell count, age.
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 1.Documented refusal of data use for research
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
PTC
Viremic PWH (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
|
No intervention (observational cohort)
|
|
Post intervention controller (PIC)
PWH 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 in MAP studies with an ART pause of less than 24 weeks.
|
No intervention (observational cohort)
|
|
Controls
non-controllers (NC) with plasma HIV-RNA >1000 c/mL after ART interruption
|
No intervention (observational cohort)
|
|
Suppressors
viremic PWH (HIV-RNA >1000c/mL) before ART initiation who became HIV-RNA <50c/mL suppressed on ART, remained on ART, and never had viral rebound.
|
No intervention (observational cohort)
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
時間枠：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.
|
1 year
|
|
Total integrated HIV DNA reservoir size in PTC and PIC before and during ATI
時間枠：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.
|
1 year
|
|
Inducible HIV reservoir size in PTC and PIC before and during ATI
時間枠：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.
|
1 year
|
|
Time from the start of ATI until first measurement of HIV RNA >50 copies/mL in PTC and PIC.
時間枠：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).
|
1 year
|
|
Time from the start of ATI until first measurement of HIV RNA >400 copies/mL in PTC and PIC.
時間枠：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).
|
1 year
|
|
Time from the start of ATI until first measurement of HIV RNA > 1000 copies/mL in PTC and PIC.
時間枠：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).
|
1 year
|
|
Number and severity of adverse events during and after ATI.
時間枠：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.
|
1 year
|
|
Biobank with samples from PTC, PIC and NC including sampling time points and material available.
時間枠：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.
|
1 year from screening
|
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スポンサー
協力者
出版物と役立つリンク
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便利なリンク
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年10月1日
一次修了 (推定)
2027年10月1日
研究の完了 (推定)
2027年12月1日
試験登録日
最初に提出
2026年5月29日
QC基準を満たした最初の提出物
2026年7月7日
最初の投稿 (実際)
2026年7月9日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月9日
QC基準を満たした最後の更新が送信されました
2026年7月7日
最終確認日
2026年7月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- MEC-2024-0338
- CO-US-985-7598 (その他の助成金/資金番号：Gilead Sciences)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
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