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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03618862
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : January 8, 2021
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.

Condition or disease Intervention/treatment
Hiv Biological: Blood sampling

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus in Circulating CD4 + T Cells Isolated From Patients With Undetectable HIV Viremia Under cART
Actual Study Start Date : January 18, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Intervention Details:
  • Biological: Blood sampling
    Peripheral venous blood collection of 56 mL during a sampling required by routine monitoring of human immunodeficiency virus infection.

Primary Outcome Measures :
  1. Reactivation of latent proviruses [ Time Frame: 1 day ]

    The primary endpoint of the study is the presence or absence of reactivation of latent proviruses present in quiescent CD4 + T cells purified from peripheral venous blood following treatment of these cells with Farnesoid X receptor agonists.

    This is a composite endpoint because the reactivation will be determined qualitatively, virus production or not after treatment, and quantitatively, level of production of infectious and / or defective viruses.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
human immunodeficiency positive patients under cART.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03618862

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Contact: Tristan FERRY, Pr 04 72 07 11 07 ext +33
Contact: Patrice ANDRE, Pr 04 37 28 23 27 ext +33

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Service des maladies infectieuses et tropicales - Hôpital de la Croix Rousse - GHN Recruiting
Lyon, France, 69004
Contact: Tristan FERRY, Pr    04 72 07 11 07 ext +33   
Principal Investigator: Tristan FERRY, Pr         
Sub-Investigator: Christian CHIDIAC, Pr         
Sponsors and Collaborators
Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon Identifier: NCT03618862    
Other Study ID Numbers: 69HCL18_0370
First Posted: August 7, 2018    Key Record Dates
Last Update Posted: January 8, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No