Switch to TAF+FTC+BIC in HIV-1-infected Patients Over 65 Years Old at Risk of Polymedication

Study Overview
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Brief Summary
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Patients infected and living with HIV are getting older and have more and more non-HIV co-morbidities. These expose them to polypharmacy that increases the risk of pharmacological interaction. Bictegravir, co-formulated with emtricitabine (FTC) and tenofovir alafenamide (TAF) (BIKTARVY) a new generation integrase inhibitor with a high genetic barrier and had no drug interaction may be a treatment of choice for participant over 65 years old who are HIV infected . BIKTARVY improve adherence and quality of life; and on the other hand it would limit the risks of pharmacological interaction. In addition, the use of TAF reducing the risk of long-term renal toxicity and adverse effects on bone would be of interest in this aging population and more at risk of osteoporosis.

Detailed Description
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HIV-1-infected patients over 65 years old at risk of polymedication HIV-1-infected adults aged ≥ 65 years who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a regimen containing a pharmacokinetic enhancer as ritonavir or cobicistat Evaluate the antiviral efficacy of 24 weeks treatment with the fixed dose combination(FDC) of TAF/FTC/BIC

Official Title
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Switch to Tenofovir Alafenamide (TAF), Emtricitabine (FTC), Bictegravir (BIC)(Biktarvy®) in HIV-1-infected Patients Over 65 Years Old at Risk of Polymedication

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1-infected patient Age > 65 years old Plasma HIV RNA ≤ 50 copies/mL for ≥ 6 months: one blip between 50 et 200 cp/ml is allowed in the past 6 months before screening. Currently receiving an antiretroviral regimen containing a booster, ritonavir or cobicistat No resistance mutation to integrase inhibitors on cumulative HIV RNA genotype. The reverse transcriptase resistant mutations M184V plus one TAM are allowed. If no genotype is available, DNA genotype will be performed at screening visit: no resistance mutation to integrase inhibitors, the reverse transcriptase resistant mutations M184V plus one TAM are allowed. Patient enrolled in or a beneficiary of a Social Security program (State Medical Aid or AME is not a Social Security program) Informed consent form signed by patient and investigator Exclusion Criteria: HIV-2 infection Currently receiving one of the following drugs: Hypericum perforatum, rifampicin, rifabutin, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, sucralfate, cyclosporine, primidone, ténofovir et adéfovir. Hemoglobin < 10g/dL Platelets < 100 000/mm3 Hepatic transaminases AST and ALT > 3x upper limit of normal (ULN) Severe hepatic insufficiency (Child Pugh Class C) Creatininemia clairance < 30 mL/min (MDRD) History or presence of allergy to the trial drugs or their components Patients participating in another clinical trial including an exclusion period that is still ongoing during the screening phase Patients under judicial protection due to temporarily and slightly diminished mental or physical faculties or under legal guardianship.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: open label, multicentric, non randomized<br>one arm study to evaluate the safety and efficacy of switching from ritonavir- or cobicistat- booster containing regimens to a fixed-dose combination (FDC) of tenofovir alafenamide (TAF), emtricitabine (FTC) and bictegravir (BIC) in over 65 years old HIV-1-infected patients with virological suppression. Polymedications and drug-drug interactions will be analysed. | Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet<br>* At BSL all the participants will be switched from a booster containing regimen (ritonavir or cobicistat) to TAF/FTC/BIC (BIKTARVY).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological failure is defined by plasma HIV RNA > 50 cps/mL on 2 following samples at 2 to 4 weeks apart | The primary outcome is the proportion of patients with virological failure at Week 24. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Charlson and Fried Score | • Assessment of co morbidities and frailty | Day 1, Week 24 and Week 48 | 
| DAD Score | • Assessment of cardio vascular risk | Day 1,Week 24 and Week 48 | 
| polymedication | • Assessment of polymedication and potential drug-drug interactions | Baseline, Week 24 and Week 48 | 
| drug interactions | • Change of drug-drug interactions | Baseline To Week 48 | 
| • adverses events | Rate of participants withdrawn from the study for grade 3 or 4 adverse event | Baseline To Week 48 | 
| therapeutic success | • Rate of therapeutic success | Week 24 and Week 48 | 
| Viral load detectable | • Rate of participants with detectable signal in case viral load is less than 20 c/ml threshold (Cobas/TaqmanHIV-1 Roche Diagnostics) at W24 and W48 | From Baseline to Week 48 | 
| Blip detectable | • Rate of participants with a blip | Baseline to Week 48 | 
| mutation | • Emergence of resistance mutations at time of virological failure | Day 1 to Week 48 | 
| immunology parameters | • Change of CD4 and CD8 cell count from BSL, | Baseline, to Week 24 and Week 48 | 
| lipid parameters | • Evolution of lipid parameters | Baseline, Week 24, Week 48 | 
| Renal parameters | Renal glomerular filtration, creatinine clearance | Baseline,Week 4,Week 12,Week 24 and Week 48 ; | 
| pharmacology | • Plasma levels of antiretroviral drugs (TAF, FTC, BIC) | Baseline, Week 12, Week 24, Week 48 | 
| Addherence | • Adherence to treatment: self-administered questionnaire | Baseline, Week 24 and Week 48 | 
| Tolerance | • Tolerance to treatment: questionnaire | Week 4, Week 24 and Week 48 | 
| Renal parameters (Urine) | urine albumin, urine creatinine, urine protein, beta-2-microglobulin and retinol binding protein | Baseline, Week 24, Week 48 |