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

NCT03622177 | Unknown

• 1 other identifier: ANRS EP65 AMVIH
• Study Type: observational
• Target: 180
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV I Infection

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Characterization of HIV reservoir of the digestive mucosa

  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

Study Arms (3)

HIV+

Procedure: biopsie; Biological: blood drawn

HIV- STI+

Procedure: biopsie

HIV- STI-

Procedure: biopsie

Interventions

biopsie PROCEDURE

Additional colorectal mucosal biopsies during rectoscopy or colonoscopy

HIV+; HIV- STI+; HIV- STI-

blood drawn BIOLOGICAL

Additional blood drawn by venepuncture

HIV+

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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)
• 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:

You may not qualify if:

• \- 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)
• Person under legal guardianship or deprived of liberty by a judicial or administrative decision.
• Pregnant or breastfeeding women
• Replicative HCV or HBV infection

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 9, 2018
• Study Start: September 1, 2018
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2023
• Last Updated: August 9, 2018

Record last verified: 2018-08