Biomarkers for Post-treatment Control in HIV: International Study of the EU2Cure Research Consortium (Phase I) (EU2Control)
7 juli 2026 bijgewerkt door: 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.
Studie Overzicht
Toestand
Nog niet aan het werven
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Observationeel
Inschrijving (Geschat)
200
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studiecontact
- Naam: Casper Rokx
- Telefoonnummer: +31618069137
- E-mail: c.rokx@erasmusmc.nl
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Kind
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Ja
Bemonsteringsmethode
Kanssteekproef
Studie Bevolking
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.
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
|---|---|
|
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)
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Medewerkers
Publicaties en nuttige links
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Nuttige links
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Geschat)
1 oktober 2026
Primaire voltooiing (Geschat)
1 oktober 2027
Studie voltooiing (Geschat)
1 december 2027
Studieregistratiedata
Eerst ingediend
29 mei 2026
Eerst ingediend dat voldeed aan de QC-criteria
7 juli 2026
Eerst geplaatst (Werkelijk)
9 juli 2026
Updates van studierecords
Laatste update geplaatst (Werkelijk)
9 juli 2026
Laatste update ingediend die voldeed aan QC-criteria
7 juli 2026
Laatst geverifieerd
1 juli 2026
Meer informatie
Termen gerelateerd aan deze studie
Andere studie-ID-nummers
- MEC-2024-0338
- CO-US-985-7598 (Ander subsidie-/financieringsnummer: Gilead Sciences)
Plan Individuele Deelnemersgegevens (IPD)
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NEE
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