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Intestinal Tissue-Resident Memory T Cells and HIV-1 Persistence During Antiretroviral Therapy (ANRSGALT-2)

14 juni 2026 bijgewerkt door: ANRS, Emerging Infectious Diseases

Intestinal Tissue-Resident Memory T Cells in HIV-1 Infection: Mechanisms Involved in Their Depletion and Role in Viral Persistence During Antiretroviral Therapy

The study aims to better characterize intestinal tissue-resident memory T cells (TRM) in people living with HIV-1 receiving suppressive antiretroviral therapy (ART). TRM cells are key components of tissue immunity and may contribute to HIV-1 persistence within the intestinal mucosa, a major viral reservoir. The phenotypic, transcriptomic, and functional characteristics of intestinal CD4+ and CD8+ TRM cells, their susceptibility to HIV-1 infection, and their potential role as viral reservoirs will be investigated. Blood samples and additional colonic biopsies obtained during routine clinically indicated colonoscopy will be collected from HIV-1-infected participants and HIV-seronegative controls.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Tissue-resident memory T lymphocytes (TRM) are a specialized population of memory T cells that reside permanently within tissues and play a central role in local immune defense. In HIV-1 infection, the intestinal mucosa represents a major site of viral replication, immune dysfunction, and long-term viral persistence despite effective antiretroviral therapy (ART). Intestinal CD4+ T cells are highly susceptible to HIV-1 infection and undergo profound depletion early during infection, while incomplete immune restoration persists under ART.

Emerging evidence suggests that intestinal TRM CD4+ cells may be particularly susceptible to HIV-1 infection and may contribute to the maintenance of viral reservoirs because of their long lifespan and tissue retention properties. In parallel, TRM CD8+ cells may participate in local antiviral immune responses, although their functions may be impaired in the chronic inflammatory environment associated with HIV infection.

The objectives of this physiopathological study are to improve understanding of the mechanisms involved in defective restoration of intestinal TRM populations during suppressive ART and to evaluate the contribution of TRM CD4+ cells to HIV-1 persistence. Exploratory objectives include the phenotypic, transcriptomic, and functional characterization of intestinal TRM CD4+ and CD8+ cells; assessment of the susceptibility of intestinal TRM CD4+ cells to HIV-1 infection; evaluation of their role as viral reservoirs, including intact proviruses; and investigation of mechanisms regulating tissue retention and recirculation of ex-TRM cells in the intestinal mucosa.

This is a monocentric interventional physiopathological study with minimal risks and constraints (RIPH2). The study will enroll 20 people living with HIV-1 receiving suppressive ART and 10 HIV-seronegative controls matched for age and sex. Participants will be recruited among individuals undergoing routine colonoscopy, particularly for colorectal cancer screening indications. Study procedures consist of additional colonic mucosal biopsies collected during the clinically indicated colonoscopy and blood sampling performed on the day of the procedure.

Studietype

Ingrijpend

Inschrijving (Geschat)

30

Fase

  • Niet toepasbaar

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

Studie Contact Back-up

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

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Ja

Beschrijving

I - Inclusion criteria

1 - Group 1: People Living With HIV-1

  • Age ≥ 18 years
  • Documented HIV-1 infection
  • Continuous suppressive antiretroviral therapy initiated during chronic infection for at least 12 months
  • Plasma HIV-1 RNA ≤ 50 copies/mL for at least 6 months under ART (one isolated blip ≤ 200 copies/mL allowed)
  • Blood CD4+ T-cell count ≥ 350 cells/mm³
  • Clinically indicated colonoscopy independent of the research protocol
  • Affiliation with a social security system

  • Written informed consent obtained before any study-specific procedure

    2- Group 2: HIV-Seronegative Controls

  • Age ≥ 18 years
  • HIV-seronegative status
  • Clinically indicated colonoscopy independent of the research protocol
  • Affiliation with a social security system
  • Written informed consent obtained before any study-specific procedure

II - Exclusion Criteria

  1. Group 1: People Living With HIV-1

    • HIV-2 infection
    • Inflammatory bowel disease (Crohn's disease or ulcerative colitis) or celiac disease
    • Platelet count < 50 G/L or uncorrectable coagulation disorders contraindicating biopsies
    • Decompensated cirrhosis
    • History of lymphoma
    • Participation in an HIV vaccine or immunotherapy study
    • Pregnant or breastfeeding women
    • Participation in another clinical study with an ongoing exclusion period
    • Vulnerable individuals, including minors, individuals under guardianship, or persons deprived of liberty

  2. Group 2: HIV-Seronegative Controls

    • HIV-1 or HIV-2 infection
    • Refusal to undergo HIV serology testing
    • Inflammatory bowel disease (Crohn's disease or ulcerative colitis) or celiac disease
    • Platelet count < 50 G/L or uncorrectable coagulation disorders contraindicating biopsies
    • Decompensated cirrhosis
    • History of lymphoma
    • Pregnant or breastfeeding women
    • Participation in another clinical study with an ongoing exclusion period
    • Vulnerable individuals, including minors, individuals under guardianship, or persons deprived of liberty

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

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: HIV-1-Infected Participants Receiving Suppressive Antiretroviral Therapy
Participants living with HIV-1 receiving suppressive antiretroviral therapy (ART) and undergoing clinically indicated colonoscopy will undergo blood sampling and additional colonic mucosal biopsies for immunological and virological analyses.
Procedure: Colonic Mucosal Biopsies
Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
Andere namen:
  • Bloedafname
Experimenteel: HIV-Seronegative Controls
HIV-seronegative participants undergoing clinically indicated colonoscopy will undergo blood sampling and additional colonic mucosal biopsies for immunological analyses.
Procedure: Colonic Mucosal Biopsies
Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
Andere namen:
  • Bloedafname

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Frequency and Immunophenotypic Profile of Intestinal CD4+ and CD8+ Tissue-Resident Memory T Cells Measured by Multiparameter Flow Cytometry
Tijdsspanne: Day 1
Frequency and expression of tissue-resident memory T-cell markers (CD69, CD103, CCR7, S1PR1), differentiation markers (CD45RA/RO, CD27, CD28), survival markers (CD127, TCF-1), activation and exhaustion markers (HLA-DR, CD38, CD57, KLRG1, CD101, PD-1, TIGIT, TIM-3, CD39), and homing markers (CD49d, β7, CCR5, CCR6, CXCR3, CXCR6, CX3CR1) on intestinal CD4+ and CD8+ T cells measured by multiparameter flow cytometry on colonic mucosal biopsy specimens.
Day 1

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Single-Cell Transcriptomic and T-Cell Receptor Repertoire Profiles of Intestinal Tissue-Resident Memory T Cells Measured by CITE-seq
Tijdsspanne: Day 1
Single-cell transcriptomic profiles and T-cell receptor repertoire of intestinal CD4+ and CD8+ tissue-resident memory T cells measured using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).
Day 1
Total and Intact HIV-1 Proviral DNA Levels in Intestinal CD4+ Tissue-Resident Memory T Cells Measured by Multiplex ddPCR Intact Proviral DNA Assay (IPDA)
Tijdsspanne: Day 1
Quantification of total and intact HIV-1 proviral DNA in intestinal CD4+ tissue-resident memory T cells isolated from colonic mucosal biopsy specimens using multiplex droplet digital PCR Intact Proviral DNA Assay (IPDA).
Day 1
Cytokine Production, Degranulation, and Proliferative Capacity of Intestinal Tissue-Resident Memory T Cells Measured by Functional Flow Cytometry Assays
Tijdsspanne: Day 1
Production of IL-2, IFN-γ, TNF-α, IL-10, IL-17, granzyme, and perforin, together with proliferative capacity following antigenic stimulation, measured in intestinal tissue-resident memory T cells using functional flow cytometry assays.
Day 1

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

ANRS, Emerging Infectious Diseases

Onderzoekers

  • Hoofdonderzoeker: Pierre Delobel, MD, PhD, University Hospital of Toulouse

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 augustus 2026

Primaire voltooiing (Geschat)

31 juli 2028

Studie voltooiing (Geschat)

31 juli 2030

Studieregistratiedata

Eerst ingediend

10 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

14 juni 2026

Eerst geplaatst (Werkelijk)

18 juni 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

14 juni 2026

Laatst geverifieerd

1 juni 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ANRS 00853-R-PR GALT-2

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

Individual participant data collected during the study will not be made publicly available. Access to study data and biological samples may be considered upon reasonable request and in accordance with applicable regulations, institutional policies, participant consent, and sponsor approval.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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