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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05222945
• Other study ID #: ANRS EP69 BICTEVOIR
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 1, 2022
• Est. completion date: March 1, 2024

Study information

• Verified date: January 2022
• Source: ANRS, Emerging Infectious Diseases
• Contact: Laura NAILLER
• Phone: +33 153 94 80 64
• Email: laura.nailler[@]anrs.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 34
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Other:
• Biopsies and bloood samplings
blood samples, rectal biopsies, nodes biopsies, cutaneous fat tissues biopsies, semen sample

Locations

Country	Name	City	State
France	Antoine-Beclere Hospita	Clamart
France	Bicetre Hospital	Le Kremlin-Bicêtre
France	Hotel Dieu Hospital	Paris
France	Necker Hospital	Paris
France	Pitie Salpetriere Hospital	Paris
France	Saint Antoine Hospital	Paris

Sponsors (2)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases	Gilead Sciences

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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