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
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Pierre Delobel, MD, PhD
- 전화번호: +33 5 61 77 75 08
- 이메일: delobel.p@chu-toulouse.fr
연구 연락처 백업
- 이름: Marcia Trumeau, MS
- 이메일: marcia.trumeau@anrs.fr
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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.
다른 이름들:
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실험적: 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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Frequency and Immunophenotypic Profile of Intestinal CD4+ and CD8+ Tissue-Resident Memory T Cells Measured by Multiparameter Flow Cytometry
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Single-Cell Transcriptomic and T-Cell Receptor Repertoire Profiles of Intestinal Tissue-Resident Memory T Cells Measured by CITE-seq
기간: 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)
기간: 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
기간: 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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공동 작업자 및 조사자
수사관
- 수석 연구원: Pierre Delobel, MD, PhD, University Hospital of Toulouse
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- ANRS 00853-R-PR GALT-2
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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