Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus (FXReservoir)
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|ClinicalTrials.gov Identifier: NCT03618862|
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : March 30, 2020
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|
|Study Type :||Observational|
|Estimated Enrollment :||40 participants|
|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 :||January 2021|
|Estimated Study Completion Date :||January 2021|
- Biological: Blood sampling
Peripheral venous blood collection of 56 mL during a sampling required by routine monitoring of human immunodeficiency virus infection.
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT03618862
|Contact: Tristan FERRY, Pr||04 72 07 11 07 ext +email@example.com|
|Contact: Patrice ANDRE, Pr||04 37 28 23 27 ext +firstname.lastname@example.org|
|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 email@example.com|
|Principal Investigator: Tristan FERRY, Pr|
|Sub-Investigator: Christian CHIDIAC, Pr|