Clinical trial NCT03622177: Role of the IL33/Amphiregulin Pathway as a Potential Therapeutic Target in HIV Infection
Official title: Role of the IL33/Amphiregulin Pathway as a Potential Therapeutic Target in HIV Infection : a Prospective Cross-sectional Observational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: HIV I Infection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2018-08-09
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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

Primary outcomes:
measure: Quantification of amphiregulin plasma levels
timeFrame: through study completion, an average of 1 year
measure: Phenotypic characterization of gut Treg cells and CD8+ T lymphocytes (CTL) isolated from the intestinal mucosa
timeFrame: through study completion, an average of 1 year
measure: Study of fibrosis markers in the intestinal mucosa
timeFrame: through study completion, an average of 1 year
measure: In vitro functional analysis of amphiregulin from isolated CTL of the lamina propria
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Characterization of HIV reservoir of the digestive mucosa
timeFrame: through study completion, an average of 1 year
measure: Determination of antiretroviral drugs levels in digestive tissue and in plasma and correlation between antiretroviral drugs levels and viral reservoir and lymphocyte phenotype
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
Study officials:
References: