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

HIV I Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03622177
• Other study ID #: ANRS EP65 AMVIH
• Status: Not yet recruiting
• Start date: September 2018
• Est. completion date: September 2023

Study information

• Verified date: August 2018
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: September 2023
• Est. primary completion date: September 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV I Infection
• HIV Infections
• Infection

Intervention

Procedure:
• biopsie
Additional colorectal mucosal biopsies during rectoscopy or colonoscopy

Biological:
• blood drawn
Additional blood drawn by venepuncture

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phenotypic characterization of gut Treg cells and CD8+ T lymphocytes (CTL) isolated from the intestinal mucosa		through study completion, an average of 1 year
Primary	Study of fibrosis markers in the intestinal mucosa		through study completion, an average of 1 year
Primary	In vitro functional analysis of amphiregulin from isolated CTL of the lamina propria		through study completion, an average of 1 year
Secondary	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
Secondary	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