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

ANRS, Emerging Infectious Diseases180 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

180

Conditions

HIV I Infection

Interventions

biopsiePROCEDURE

Additional colorectal mucosal biopsies during rectoscopy or colonoscopy

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.