Intestinal Tissue-Resident Memory T Cells and HIV-1 Persistence During Antiretroviral Therapy (ANRSGALT-2)
Intestinal Tissue-Resident Memory T Cells in HIV-1 Infection: Mechanisms Involved in Their Depletion and Role in Viral Persistence During Antiretroviral Therapy
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Pierre Delobel, MD, PhD
- Número de teléfono: +33 5 61 77 75 08
- Correo electrónico: delobel.p@chu-toulouse.fr
Copia de seguridad de contactos de estudio
- Nombre: Marcia Trumeau, MS
- Correo electrónico: marcia.trumeau@anrs.fr
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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
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
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: 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.
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Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
Otros nombres:
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Experimental: HIV-Seronegative Controls
HIV-seronegative participants undergoing clinically indicated colonoscopy will undergo blood sampling and additional colonic mucosal biopsies for immunological analyses.
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Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Frequency and Immunophenotypic Profile of Intestinal CD4+ and CD8+ Tissue-Resident Memory T Cells Measured by Multiparameter Flow Cytometry
Periodo de tiempo: Day 1
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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.
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Day 1
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Single-Cell Transcriptomic and T-Cell Receptor Repertoire Profiles of Intestinal Tissue-Resident Memory T Cells Measured by CITE-seq
Periodo de tiempo: Day 1
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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).
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Day 1
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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)
Periodo de tiempo: Day 1
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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).
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Day 1
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Cytokine Production, Degranulation, and Proliferative Capacity of Intestinal Tissue-Resident Memory T Cells Measured by Functional Flow Cytometry Assays
Periodo de tiempo: Day 1
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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.
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Day 1
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Pierre Delobel, MD, PhD, University Hospital of Toulouse
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ANRS 00853-R-PR GALT-2
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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