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

14. juni 2026 oppdatert av: 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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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

Intervensjonell

Registrering (Antatt)

30

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Ja

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Fremgangsmåte: Colonic Mucosal Biopsies
Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
Andre navn:
  • Blodprøvetaking
Eksperimentell: HIV-Seronegative Controls
HIV-seronegative participants undergoing clinically indicated colonoscopy will undergo blood sampling and additional colonic mucosal biopsies for immunological analyses.
Fremgangsmåte: Colonic Mucosal Biopsies
Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
Andre navn:
  • Blodprøvetaking

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Frequency and Immunophenotypic Profile of Intestinal CD4+ and CD8+ Tissue-Resident Memory T Cells Measured by Multiparameter Flow Cytometry
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Single-Cell Transcriptomic and T-Cell Receptor Repertoire Profiles of Intestinal Tissue-Resident Memory T Cells Measured by CITE-seq
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

ANRS, Emerging Infectious Diseases

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. august 2026

Primær fullføring (Antatt)

31. juli 2028

Studiet fullført (Antatt)

31. juli 2030

Datoer for studieregistrering

Først innsendt

10. juni 2026

Først innsendt som oppfylte QC-kriteriene

14. juni 2026

Først lagt ut (Faktiske)

18. juni 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

18. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

14. juni 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ANRS 00853-R-PR GALT-2

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

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.

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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