Role of the IL33/Amphiregulin Pathway as a Potential Therapeutic Target in HIV Infection

Study Overview
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Brief Summary
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Interleukin33 organize local immune reactions, especially at epithelial barriers. ST2 is the IL33 receptor. The sST2 rate is higher for patient living with HIV and is an independent predictable factor of mortality. Interleukin33 induce tissue Treg ST2+ lymphocytes proliferation and amphireguline production. Amphireguline is member of epithelial growth factors family, which contributes to tissue repair, and fibrose. Amphireguline also helps immunosuppressives functions. Targetting amphiregulin for people living with HIV who has poor restauration of LTCD4+ could be a future therapy.

Official Title
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Role of the IL33/Amphiregulin Pathway as a Potential Therapeutic Target in HIV Infection : a Prospective Cross-sectional Observational Study

Conditions
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HIV I Infection

Intervention / Treatment
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* Procedure: biopsie
* Biological: blood drawn


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1: HIV-infected subjects HIV-1 infection Age ≥ 18 years old CD4 count≥ 100/mm3 Receiving an active antiretroviral treatment (plasma HIV viral load ≤ 50 copies/ml) Subjects needing an STI screening for routine care including rectal biopsy (independently of the current study protocol) NB : an additional inclusion criteria for the Group 1 will be defined after the phase 0 which will define two levels of fibrosis (low / high) Group 2: controls not infected with HIV needing a rectoscopy for an STI screening HIV negative Age ≥ 18 years old Subjects needing an STI screening for routine care including rectal biopsy (independently of the current study protocol) Group 3: controls not infected with HIV needing a colonoscopy HIV negative Age ≥ 18 years old Subjects needing a colonoscopy with colorectal biopsy as part of routine care (independently of the current study protocol) For the 3 groups: Inclusion criteria Affiliated or beneficiary of a Social Security coverage Free, informed and written consent, signed by the participant and the investigator (at the latest on the day of pre-inclusion and before any examination carried out within the framework of the trial) Exclusion Criteria for the 3 groups - HIV-2 infection or HIV-1 & HIV-2 co-infection Active infection or cancer Contraindication to rectal biopsies (coagulation disorders, anticoagulation therapy, anorectal surgery, inflammatory bowel disease, post-radial rectitis) Subject participating in another research evaluating other treatments with an exclusion period ongoing at the screening visit. Person under legal guardianship or deprived of liberty by a judicial or administrative decision. Pregnant or breastfeeding women Replicative HCV or HBV infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV+<br> | Procedure: biopsie<br>* Additional colorectal mucosal biopsies during rectoscopy or colonoscopy<br>Biological: blood drawn<br>* Additional blood drawn by venepuncture<br>|
| HIV- STI+<br> | Procedure: biopsie<br>* Additional colorectal mucosal biopsies during rectoscopy or colonoscopy<br>|
| HIV- STI-<br> | Procedure: biopsie<br>* Additional colorectal mucosal biopsies during rectoscopy or colonoscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of amphiregulin plasma levels | Quantification of amphiregulin plasma levels in HIV-infected subjects and correlation these levels with blood TCD4 cell count and clinical parameters (cardiac diastolic dysfunction, organ dysfunctions likely to be secondary to fibrosis phenomena) recorded in the CARDAMONE cohort. | through study completion, an average of 1 year | 
| Phenotypic characterization of gut Treg cells and CD8+ T lymphocytes (CTL) isolated from the intestinal mucosa |  | through study completion, an average of 1 year | 
| Study of fibrosis markers in the intestinal mucosa |  | through study completion, an average of 1 year | 
| In vitro functional analysis of amphiregulin from isolated CTL of the lamina propria |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of HIV reservoir of the digestive mucosa | (i) Analysis at the blood and digestive compartment (rectum) for different CD4 CD32a T lymphocyte populations, marker of the viral reservoir; (ii) Quantification HIV DNA and the HIV reservoir competent for replication from blood and gut | through study completion, an average of 1 year | 
| Determination of antiretroviral drugs levels in digestive tissue and in plasma and correlation between antiretroviral drugs levels and viral reservoir and lymphocyte phenotype |  | through study completion, an average of 1 year |