Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus

NCT ID: NCT03618862

Last Updated: 2021-07-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 38 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-18
• Study Completion Date: 2021-07-16

Brief Summary

The Farnesoid X receptor (FXR) is a nuclear receptor that controls the transcription of many genes involved in lipid and glucose metabolism. A recent study opens the hypothesis that Farnesoid X receptor also participates in deoxyribonucleic acid repair mechanisms and possibly in the fight against cell invasion by foreign genomes. This hypothesis implied that modulation of Farnesoid X receptor by ligands could modify Human Immunodeficiency Virus replication. The results of in vitro studies with Human Immunodeficiency Virus-infected cell lines indicate that indeed the modulation of Farnesoid X receptor activity by its ligands induces stimulation of virus production rapidly followed by cell death; the overall effect is therefore antiviral. Farnesoid X receptor ligands have also shown an effect on the reactivation of proviruses in cellular models of viral latency studies. This last data raises the hope of being able to intervene on the reservoir of Human Immunodeficiency Virus.

It is therefore crucial to confirm on quiescent CD4 + T lymphocytes of patients whose viral load is controlled by antiretroviral treatment combining several antiretrovirals the results obtained with the in vitro models.

Providing proof of concept that Farnesoid X receptor agonists can reactivate latent proviruses will open new therapeutic perspectives for attacking the Human Immunodeficiency Virus reservoir with a view to achieving a functional cure for Acquired Immune Deficiency Syndrome. The objective of the study is to confirm ex vivo the data obtained in vitro with cellular models and laboratory viral strains. It is therefore necessary to show that Farnesoid X receptor agonists can reactivate latent viruses or proviruses present in quiescent CD4 + T circulating lymphocytes prepared from venous blood of HIV-positive patients under cART. Human Immunodeficiency Virus-positive patients will be any patients, irrespective of the viral genotype, who initiated antiretroviral therapy, regardless of the combination of antiretrovirals, away from primary infection, when they already had a complete western blot, indicating an evolution of the infection without treatment and constitution of an already evolved reservoir. Patients will have had an undetectable viral load since initiation of treatment with a follow-up of at least one year and will have at least 500 CD4 + T lymphocytes / mm3.

Conditions

Hiv

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Blood sampling

Peripheral venous blood collection of 56 mL during a sampling required by routine monitoring of human immunodeficiency virus infection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• human immunodeficiency virus infected patients
• T CD4 > 500/mm3. Viral load undetectable for more than a year under stable treatment. No history of virological failure.
• under first line cART treatment
• Indetectable viral load

Exclusion Criteria

• Acute or chronic anemias.-
• Acute infections, fever
• Vaccination in the two months preceding inclusion.

• 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

Locations

Service des maladies infectieuses et tropicales - Hôpital de la Croix Rousse - GHN

Lyon, , France

Countries

France

Other Identifiers

69HCL18_0370

Identifier Type: -

Identifier Source: org_study_id