Biomarkers for Post-treatment Control in HIV: International Study of the EU2Cure Research Consortium (Phase I) (EU2Control)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV
• Intervention / Treatment: Other: No Intervention: Observational Cohort

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Casper Rokx; Phone Number: +31618069137; Email: c.rokx@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

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.

Description

Inclusion Criteria:

1. 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.
2. 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.
3. Controls: non-controllers (NC) with plasma HIV-RNA >1000 c/mL after ART interruption.
4. 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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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	Other: No Intervention: Observational Cohort; 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.	Other: No Intervention: Observational Cohort; No intervention (observational cohort)
Controls; non-controllers (NC) with plasma HIV-RNA >1000 c/mL after ART interruption	Other: No Intervention: Observational Cohort; 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.	Other: No Intervention: Observational Cohort; No intervention (observational cohort)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI	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	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	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.	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.	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.	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.	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.	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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: IRCCS San Raffaele; Radboud University Medical Center; Charite University, Berlin, Germany; Oslo University Hospital; Hospital Universitari Vall d'Hebron Research Institute; Imperial College London; University of Aarhus; University of Oxford; Guy's and St Thomas' NHS Foundation Trust; Centre Hospitalier Universitaire Vaudois; Institut Pasteur; University Hospital, Ghent; Pomeranian Medical University Szczecin; University Ghent; Medical University of Warsaw; IrsiCaixa; Chelsea and Westminster Hospital, UK; European Aids Treatment Group (EATG), Brussels, Belgium; Fundació Lluita contra les Infeccions; EU2Cure consortium

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: HIV; biomarkers; biobank; Post-treatment control; Post-intervention control
• Other Study ID Numbers: MEC-2024-0338; CO-US-985-7598 (Other Grant/Funding Number: Gilead Sciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO