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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Aïda BENALYCHERIF; Phone Number: 331 40256365; Email: aida.benalycherif@fondation-imea.org

Study Locations

• France
  • Marseille, France, 13009
    • Recruiting
    • Hôpital Sainte Marguerite
    • Contact: ISABELLE POZOT MARTIN; Phone Number: 334 0491746163; Email: isabelle.poizot@mail.ap-hm.fr
    • Principal Investigator: Isabelle POIZOT-MARTIN, MD,PHD
  • Nantes, France, 44093
    • Recruiting
    • Hôpital Hotel Dieu
    • Contact: CLOTILDE ALLAVENA; Phone Number: 332 40083110; Email: clotilde.allavena@chu-nantes.fr
  • Nice, France
    • Recruiting
    • Hôpital l'Archet
    • Contact: Alissa NAQVI
    • Contact: Email: naqvi.a@chu-nice.fr
  • Paris, France, 75018
    • Recruiting
    • Bichat Hospital
    • Contact: Valentina ISERNIA, MD; Phone Number: 331 40257057; Email: valentina.isernia@aphp.fr
    • Contact: BAO PHUNG, MD; Phone Number: 331 40257057; Email: bao.phung@aphp.fr
    • Principal Investigator: YAZDAN YAZDANPANAH, MD,PHD
  • Paris, France, 75004
    • Recruiting
    • Hôpital Hotel Dieu
    • Contact: Laurence WEISS
    • Contact: Email: laurence.weiss@aphp.fr
  • Saint-Nazaire, France
    • Active, not recruiting
    • CH de Saint Nazaire
  • Tourcoing, France, 59208
    • Recruiting
    • Hôpital Gustave Dron
    • Contact: FAIZA AJANA; Phone Number: 333 0320694617; Email: fajana@ch-tourcoing.fr
    • Principal Investigator: FAIZA AJANA
  • Tours, France
    • Active, not recruiting
    • Hôpital Bretonneau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 63 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: open label, multicentric, non randomized; 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; At BSL all the participants will be switched from a booster containing regimen (ritonavir or cobicistat) to TAF/FTC/BIC (BIKTARVY).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
• Collaborators: Pierre and Marie Curie University

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Actual): December 20, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 8, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine
• Other Study ID Numbers: IMEA 057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No