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

Study Overview
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Brief Summary
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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.

Detailed Description
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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)

Official Title
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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

Conditions
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HIV-1-infection

Intervention / Treatment
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* Other: Biopsies and bloood samplings


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral cartography, Viral reservoir, Antiretroviral treatments diffusion