Biomarkers for Post-treatment Control in HIV: International Study of the EU2Cure Research Consortium (Phase I) (EU2Control)
7. juli 2026 opdateret af: 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.
Studieoversigt
Status
Ikke rekrutterer endnu
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Observationel
Tilmelding (Anslået)
200
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Casper Rokx
- Telefonnummer: +31618069137
- E-mail: c.rokx@erasmusmc.nl
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Ja
Prøveudtagningsmetode
Sandsynlighedsprøve
Studiebefolkning
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.
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
|
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)
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Hjælpsomme links
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Anslået)
1. oktober 2026
Primær færdiggørelse (Anslået)
1. oktober 2027
Studieafslutning (Anslået)
1. december 2027
Datoer for studieregistrering
Først indsendt
29. maj 2026
Først indsendt, der opfyldte QC-kriterier
7. juli 2026
Først opslået (Faktiske)
9. juli 2026
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
9. juli 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
7. juli 2026
Sidst verificeret
1. juli 2026
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- MEC-2024-0338
- CO-US-985-7598 (Andet bevillings-/finansieringsnummer: Gilead Sciences)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
INGEN
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