IL-23/IL-12 Imbalance and T Lymphocyte Polarization in HIV Infection

HIV Reservoirs Clinical Trial

— INTESTIPAX  

Official title:

ANRS RF002 Intestipax : Interleukin-23 (IL-23)/Interleukin-12 (IL-12) Imbalance and T Lymphocyte Polarization in HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01942655
• Other study ID #: ANRS RF002 INTESTIPAX
• Status: Completed
• Phase: N/A
• Start date: June 1, 2014
• Est. completion date: March 1, 2018

Study information

• Verified date: April 2019
• 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: Interventional

Clinical Trial Summary

Progressive HIV or HIV infection seems to be related to a preferential loss of CD4+ T lymphocytes, especially Th17+, within the mucosal intestinal lymphoid tissue, and with intestinal mucosal damage and bacterial product translocation, which correlates with the hyperactivation of the immune system, therefore with CD4+ T cell loss and prognosis. The objectives of this project are to investigate the correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to study the polarization, infection or depletion of intestinal Th17 ex vivo. The investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.

Description:

Th17 lymphocytes fight bacterial and fungal intestinal infections. Under combined antiretroviral therapy, even if the plasma viral load is undetectable, hyperactivation can persist, inducing localized replication from reservoirs. In humans, Th17 lymphocyte differentiation and expansion depend on IL-23. The investigators were the first to uncover an imbalance in the respective production of IL-12 and IL-23 in response to Lipopolysaccharide (LPS) in HIV-1 infected patients. IL-23 and its receptor are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD) like Crohn's disease, where the mucosa is altered by Th17 cells, inducing bacterial product translocation. IBD can be efficiently treated by antibodies directed against Tumor Necrosis Factor-α (TNF-α) or, in current clinical trials, against the p40 chain which is shared by IL-12 and IL-23. Unfortunately, these antibodies inhibit also IL-12. IL-12 is crucial against mycobacteria, which are opportunistic in HIV-infected patients. Antibodies directed against the p19 chain of IL-23 would inhibit Th17 activation more specifically.

The investigators will collect blood and recto-colic biopsies from 15 healthy donors, 15 HIV-infected patients with a viral load higher than 5000 copies/ml and 15 patients with evolutive IBD, to establish a parallel between the two diseases.

The objectives of this project are to study if there is a correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to investigate the polarization, infection or depletion of intestinal Th17 ex vivo. Investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.

If these correlations are validated, the investigators will propose anti-IL-23 neutralizing treatment to allow Th17 and intestinal integrity to come back into balance, and therefore to break the vicious cycle of immune system hyperactivation drawn by bacterial translocation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 1, 2018
• Est. primary completion date: March 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

• Age higher than 18

• Able to give written consent

• Recto-colic biopsies prescribed for patient care

• Covered by French Health Insurance System (Social Security) (15 HIV patients with documented detectable HIV viral load in the past 6 months, 15 HIV negative patients with evolutive IBD, 15 HIV negative patients without evolutive IBD)

Exclusion Criteria:

• Absence of coverage by French Health insurance system (Social Security)

• Known progressive malignancy

• Indeterminate colitis

• Known autoimmune diseases other than IBD

• Current chemotherapy or radiotherapy

• Vulnerable populations (children, pregnant women, persons under legal guardianship, or deprived of freedom by judicial or administrative decision)

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV Reservoirs

Intervention

Other:
• Blood sample and recto-colic biopsies

Locations

Country	Name	City	State
France	Centre d'Investigation Clinique BT505, Hôpital Cochin	Paris

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)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Multiple measures : HIV viral load levels in blood and intestinal biopsies		25 months
Primary	Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies.		25 months
Secondary	Multiple measures : number of cells producing IL-23 and Th17 cells in intestinal biopsies		25 months