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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Antiretroviral Therapy; HIV-1 Infection; HIV Reservoir
• Intervention / Treatment: Procedure: Colonic Mucosal Biopsies

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre Delobel, MD, PhD; Phone Number: +33 5 61 77 75 08; Email: delobel.p@chu-toulouse.fr
• Study Contact Backup: Name: Marcia Trumeau, MS; Email: marcia.trumeau@anrs.fr

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Procedure: Colonic Mucosal Biopsies; Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.; Other Names: Blood Sampling
Experimental: 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.; Other Names: Blood Sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Immunophenotypic Profile of Intestinal CD4+ and CD8+ Tissue-Resident Memory T Cells Measured by Multiparameter Flow Cytometry	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single-Cell Transcriptomic and T-Cell Receptor Repertoire Profiles of Intestinal Tissue-Resident Memory T Cells Measured by CITE-seq	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)	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	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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Pierre Delobel, MD, PhD, University Hospital of Toulouse

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: June 10, 2026
• First Submitted That Met QC Criteria: June 14, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV-1; ART; Viral Reservoir; Mucosal Immunity; HIV Persistence; Tissue-Resident Memory T Cells; Intestinal Mucosa; CD4 T Cells
• Additional Relevant MeSH Terms: Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: ANRS 00853-R-PR GALT-2

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No