Biomarkers for Post-treatment Control in HIV: International Study of the EU2Cure Research Consortium (Phase I) (EU2Control)
7. července 2026 aktualizováno: 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.
Přehled studie
Postavení
Zatím nenabíráme
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Pozorovací
Zápis (Odhadovaný)
200
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Casper Rokx
- Telefonní číslo: +31618069137
- E-mail: c.rokx@erasmusmc.nl
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dítě
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ano
Metoda odběru vzorků
Ukázka pravděpodobnosti
Studijní populace
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.
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
|
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)
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
Časové okno: 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
Časové okno: 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
Časové okno: 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.
Časové okno: 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.
Časové okno: 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.
Časové okno: 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.
Časové okno: 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.
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Spolupracovníci
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Užitečné odkazy
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
1. října 2026
Primární dokončení (Odhadovaný)
1. října 2027
Dokončení studie (Odhadovaný)
1. prosince 2027
Termíny zápisu do studia
První předloženo
29. května 2026
První předloženo, které splnilo kritéria kontroly kvality
7. července 2026
První zveřejněno (Aktuální)
9. července 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
9. července 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
7. července 2026
Naposledy ověřeno
1. července 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další identifikační čísla studie
- MEC-2024-0338
- CO-US-985-7598 (Jiné číslo grantu/financování: Gilead Sciences)
Plán pro data jednotlivých účastníků (IPD)
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