Selection of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent HIV Proviruses

NCT ID: NCT05219916

Last Updated: 2023-03-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-12
• Study Completion Date: 2022-07-22

Brief Summary

The FXReservoir#1 study (NCT03618862) showed that certain FXR ligands reactivate latent viruses in the reservoir circulating in all HIV+ patients tested. These molecules appear as latency reversal agents (LRA) of silent viruses of the HIV reservoir. They can be part of the strategy to eradicate this reservoir, responsible for recurrences of the infection when combined anti-retroviral treatments are stopped.

Two effective leads have been identified on in vitro tests and on ex vivo reactivation using FXReservoir#1. These molecules come from a chemical library of FXR ligands developed by the Inserm team behind the discovery of a role for FXR in viral infections.

A first series of optimized molecules derived from these leads has been synthesized; these molecules, after screening on viral and ADMET (Absorption, Distribution, Metabolisme, Excretion and Toxicity) in vitro tests, must be tested ex vivo on CD4+ lymphocytes from the circulating peripheral reservoir of HIV+ patients in order to select the best molecules with LRA activity. This step is essential before considering the clinical development of an LRA.

Conditions

Human Immunodeficiency Virus I Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Adult patients infected by HIV, controlled under treatment.

Blood sample collection from HIV controlled patients during their scheduled consultation, after obtaining their non-opposition by an investigator.

Group Type: EXPERIMENTAL

Blood collection.

Intervention Type: PROCEDURE

One additional 80 mL blood collection will be collected from HIV patients during a scheduled blood collection as part of their regular follow-up.

Samples will be transported within 3-5 hours by a carrier approved for the transportation of infectious biological samples from the Croix Rousse hospital to the P3 laboratory of the Ecole Normale Supérieure, Lyon for analysis.

Interventions

Blood collection.

One additional 80 mL blood collection will be collected from HIV patients during a scheduled blood collection as part of their regular follow-up.

Samples will be transported within 3-5 hours by a carrier approved for the transportation of infectious biological samples from the Croix Rousse hospital to the P3 laboratory of the Ecole Normale Supérieure, Lyon for analysis.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Criteria relating to the population studied: patients aged 18 to 65 years old, men or women, regardless of ethnic origin.
• Nosological criteria: HIV-1 infection, documented by a complete western blot and/or a detectable viral load at the time of diagnosis, regardless of the viral subtype.
• Pathology severity and progression criteria: patients with a CD4+ count greater than 500 elements/mm3 at the last follow-up visit prior to inclusion in the study. Undetectable viral load for at least six months on stable treatment.
• Criteria relating to treatments/strategies/procedures: Current cART treatment mandatory, regardless of the combination of anti-retrovirals, effective with undetectable viral load. The number of processing lines is not limited.
• Criteria relating to regulation: Absence of opposition

Exclusion Criteria

• Criteria relating to the population studied: pregnant or breastfeeding women
• Criteria relating to contraindications to the protocol explorations:

Acute or chronic anaemias Acute infections, fever Coagulation disorders, patients taking anticoagulants

• Criteria relating to regulation: Subjects placed under judicial safeguard, guardianship or curatorship Subjects participating in another research with an ongoing exclusion period.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tristan FERRY, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

Service des maladies infectieuses et tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon

Locations

Service des maladies infectieuses et tropicales Hôpital de la Croix Rousse

Lyon, , France

Countries

France

Other Identifiers

69HCL21_0846

Identifier Type: -

Identifier Source: org_study_id