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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV I Infection
• Intervention / Treatment: Procedure: biopsie; Biological: blood drawn

• Study Type: Observational
• Enrollment (Anticipated): 180

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

people living with HIV compare to people who are not living with HIV :

- people with high burden of STI / people without burden of STI

Description

Inclusion Criteria:

1. 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)

2. 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)

3. 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV+	Procedure: biopsie; Additional colorectal mucosal biopsies during rectoscopy or colonoscopy; Biological: blood drawn; Additional blood drawn by venepuncture
HIV- STI+	Procedure: biopsie; Additional colorectal mucosal biopsies during rectoscopy or colonoscopy
HIV- STI-	Procedure: biopsie; Additional colorectal mucosal biopsies during rectoscopy or colonoscopy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: August 3, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; HIV Infections; Infections; Communicable Diseases
• Other Study ID Numbers: ANRS EP65 AMVIH

Drug and device information, study documents

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