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

• Conditions: HIV I Infection
• Interventions: Procedure: biopsie; Biological: blood drawn

• Registration Number: NCT03622177
• Lead Sponsor: ANRS, Emerging Infectious Diseases

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2018-08
• Study First Submitted: 2018-08-03
• Study First Submitted QC: 2018-08-07
• Last Update Submitted: 2018-08-07
• Study First Posted: 2018-08-09
• Last Update Posted: 2018-08-09
• Study Start: 2018-09
• Primary Completion: 2019-09
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 180

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HIV+	biopsie	-
HIV- STI-	biopsie	-
HIV+	blood drawn	-
HIV- STI+	biopsie	-

Primary Outcome Measures

Name	Time	Method
Quantification of amphiregulin plasma levels	through study completion, an average of 1 year	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.
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
Phenotypic characterization of gut Treg cells and CD8+ T lymphocytes (CTL) isolated from the intestinal mucosa	through study completion, an average of 1 year

Secondary Outcome Measures

Name	Time	Method
Characterization of HIV reservoir of the digestive mucosa	through study completion, an average of 1 year	(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
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