A Study to Determine the Cartography of Virologic Reservoir Related to Antiretroviral Concentrations in HIV-1 Chronic Patients Treated by a First Line Treatment Containing Bictégravir, Emtricitabine and Ténofovir Alafénamide

ANRS EP69 BICTEVOIR : a Prospective Study to Determine the Cartography of Virologic Reservoir Related to Antiretroviral Concentrations in HIV-1 Chronic Patients Treated by a First Line Treatment Containing Bictégravir, Emtricitabine and Ténofovir Alafénamide

The main objective of the study is to evaluate the diffusion of bictegravir and associated backbone (tenofovir alafenamide and emtricitabine) in HIV-1 chronic patients in the main putative reservoirs, namely inguinal lymph nodes, rectal, fat tissues and sperm.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Other: Biopsies and bloood samplings

Detailed Description

ANRS EP69 BICTEVOIR is an interventional pilot study, multicenter, involving the use of human biological samples.

34 HIV-1 infected male subjects, from Bicetre, La Pitié Salpêtriere, Antoine-Béclère, Necker, Hôtel-Dieu and Saint-Antoine Hospitals will be recruited.

Different samples will be performed during one single day:

• blood samples
• rectal biopsies
• nodes biopsies
• cutaneous fat tissues biopsies
• semen sample (at home)

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fatoumata Coulibaly; Phone Number: +331 44 23 61 10; Email: fatoumata.coulibay@inserm.fr
• Study Contact Backup: Name: Sophie LETROU; Phone Number: +331 40 25 65 81; Email: sophie.letrou@aphp.fr

Study Locations

• France
  • Clamart, France
    • Antoine-Beclere Hospita
    • Contact: Sophie ABGRALL
  • Le Kremlin-Bicêtre, France
    • Bicetre Hospital
    • Contact: Antoine CHERET
    • Contact: Elina TEICHER
  • Paris, France
    • Pitié Salpêtrière hospital
    • Contact: Valérie MARTINEZ
  • Paris, France
    • Necker Hospital
    • Contact: Claudine DUVIVIER
  • Paris, France
    • Hotel Dieu Hospital
    • Contact: Dominique SALMON-CERON
  • Paris, France
    • Saint Antoine Hospital
    • Contact: Karine LACOMBE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male HIV-1 infected subjects
• Age > or = 18 years old
• Currently receiving as first line a stable ARV regimen containing bictegravir (at 50 mg once a day) and two nucleoside reverse transcriptase inhibitors, tenofovir alafenamide/emtricitabine (Biktarvy)
• HIV RNA <50 Cp/mL, undetectable 6 months after treatment initiation and confirmed and 12 months after treatment initiation.
• Normal laboratory value of TP and TCA and platelets numbers at screening
• Written and informed consent signed by the person and the investigator (no later than the day of pre-inclusion and prior to any examination realized in the frame of the research / study / trial) (article L1122-1-1 of the Public Health Code)
• Person affiliated or beneficiary of a social security scheme (article L1121-11 of the Public Health Code) (State Medical Aid or AME is not a social security scheme)

Exclusion Criteria:

• Single HIV-2 infection
• Biopsies contraindication, taking anticoagulant and antiplatelet drugs are not allowed
• Haemophilia
• Symptomatic sexually transmitted infection
• Being under guardianship or trusteeship mandate for future protection
• Participate to another research involving human person, categories 1 or 2,
• Associated treatments : carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifampicin, St. John's Wort.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm composed by 34 HIV-1 infected male subjects	Other: Biopsies and bloood samplings; blood samples, rectal biopsies, nodes biopsies, cutaneous fat tissues biopsies, semen sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the diffusion of bictegravir and associated backbone (tenofovir alafenamide and emtricitabine) in sperm	Dosage of the different antiretroviral drugs molecules in sperm	At Day 0, At time T0 (before taking treatments)
Characterization of the diffusion of bictegravir and associated backbone (tenofovir alafenamide and emtricitabine) in lymph nodes	Dosage of the different antiretroviral drugs molecules in lymph nodes	At Day 0, between T1 (maximum 3 hours after tacking treatments) and T3 (8 hours after taking treatments)
Characterization of the diffusion of bictegravir and associated backbone (tenofovir alafenamide and emtricitabine) in fat tissues	Dosage of the different antiretroviral drugs molecules in fat tissues	At Day 0, between T1 (maximum 3 hours after tacking treatments) and T3 (8 hours after taking treatments)
Characterization of the diffusion of bictegravir and associated backbone (tenofovir alafenamide and emtricitabine) in rectal tissues	Dosage of the different antiretroviral drugs molecules in rectal tissues	At Day 0, T1 (maximum 3 hours after taking treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of the spatial dynamics of viral quasi-species In the different reservoirs	Analyze of the spatial dynamics of HIV-DNA and HIV-RNA from Lymphoid, rectal, genital secretion, blood, fat cells by phylogenetic analyses after sequencing Env HIV-DNA and HIV-RNA	At Day 0
Characterization of the level of the replication (RNA-HIV) in the reservoirs	Analyze and comparison of the level of viral transcription by measuring the cell-associated HIV- RNA in the different tissues and fluids: lymphoid, rectal, genital secretion, blood and fat biopsies as well as cerebrospinal fluid.	At Day 0
Characterization of the level of infection (DNA-HIV) in the reservoirs	Analyze and comparison of the reservoir level by measuring the cell-associated total HIV- DNA in the different tissues and fluids	At Day 0
Study of the mutations of resistance in the integrase gene	Description of resistance mutations in Integrase gene which could be linked to suboptimal concentrations of bictegravir	At Day 0
Description for each compartment of the relationship between exposure to therapeutic combinations and the level of infection / viral replication	Characterization of the relationship between the concentration of bictegravir and backbone drugs with the level of wild type viral replication in the different compartments. Analyze of the impact of backbone drugs associated to bictegravir on viral level production. Correlation between the level of resistant virus replication and the exposure to bictegravir and the backbone drugs. Evaluation by simulation the effect of different dosing regimen of bictegravir (including higher doses) on the level of viral replication and on resistance	At Day 0

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Antoine CHERET, Pr, Centre de Diagnostic et de Thérapeutique pluridisciplinaire CHU Pointe-à-Pitre/Abymes

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Viral cartography; Viral reservoir; Antiretroviral treatments diffusion
• Other Study ID Numbers: ANRS EP69 BICTEVOIR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No