BFTAF Elderly Switch Study

NCT05243602 | Completed Phase 4 DMC

• 1 other identifier: BFTAF
• Study Type: interventional
• Target: 520
• Locations: 1 country
• Sites: 2

Brief Summary

BACKGROUND: Current Kenya National Anti-retroviral (ARV) Guidelines and World Health Organization (WHO) Guidelines recommend first-line therapy of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and dolutegravir (DTG) for adult people living with HIV (PLHIV). This regimen has limitations, particularly for the aging PLHIV who are more likely to have pre-existing comorbidities and higher risk of developing comorbidities, including osteopenia, osteoporosis, and renal insufficiency. Abacavir, the preferred alternative nucleoside reverse transcriptase inhibitor (NRTI) in Kenya, is associated with increased cardiovascular risk that also limits its use in elderly populations. B/F/TAF is highly efficacious, well tolerated, co-formulated in a small pill, and does not have the same bone, renal or cardiovascular risks associated with currently recommended regimens in Kenya. We are not aware of any clinical trial to date that has been fully powered to compare ARV regimens for the increasing population of elderly PLHIV. BROAD OBJECTIVE: We will compare the efficacy, safety, and impact on bone mineral density of switching to B/F/TAF to that of remaining on current ARV regimen in a population of elderly patients (60 years old or greater) with no prior confirmed treatment failure in Kenya.

Conditions

HIV-1-infection

Keywords

HIV; Bictegravir; Tenofovir alafenamide; Switch; Elderly; Non-inferiority; First-line

Outcome Measures

Primary Outcomes (2)

• Virologic failure at week 48

  Proportion of participants with HIV-1 RNA ≥ 50 copies/ml at week 48 (by US Food and Drug Administration (FDA) snapshot algorithm)

  48 weeks

• Change in BMD

  Mean percentage change in lumbar spine BMD from baseline to week 48

  48 weeks

Secondary Outcomes (19)

• Virologic failure at week 24

  24 and 96 weeks

• Treatment success

  24, 48 and 96 weeks

• Change in BMD

  24 and 96 weeks

• Change in total hip BMD

  24, 48 and 96 weeks

• Change in fracture risk as measured using the fracture risk assessment tool (FRAX)

  24, 48 and 96 weeks

Study Arms (2)

Switch to B/F/TAF

EXPERIMENTAL

Participants in this arm will switch from their current ARV regimen to the study drug B/F/TAF. This is an oral drug administered once daily for the duration of the study.

Drug: Switch to B/F/TAF

Continue current regimen

ACTIVE COMPARATOR

Participants in this arm will be maintained on their pre-enrollment ARV regimen for the duration of the study.

Drug: Continue current regimen

Interventions

Switch to B/F/TAF DRUG

This is a combined pill containing 50mg of bictegravir, 200mg of emtricitabine and 25mg of tenofovir alafenamide

Also known as: Biktarvy

Switch to B/F/TAF

Continue current regimen DRUG

Participants will continue taking the same ARV regimen they were on before enrollment with no change in drug or dosage for the duration of the trial

Also known as: Control

Continue current regimen

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to understand and comply with the protocol requirements, instructions and restrictions
• Able and willing to give informed consent
• Age 60 years or above
• Documented HIV-1 infection as confirmed by HIV-antibody testing as per the Kenya National Guidelines
• Has been receiving an ARV regimen for at least 24 weeks
• Documented HIV-1 RNA viral load \< 50 copies/ml at least 12 weeks prior to enrollment and no viral rebound between the first viral load \< 50 copies/ml and the screening viral load
• HIV-1 RNA viral load \< 50 copies/ml at screening (within 28 days prior to enrollment)

You may not qualify if:

• Confirmed treatment failure as defined by two consecutive HIV-1 RNA viral loads ≥ 50 copies/ml separated by at least 2 weeks, after at least 6 months on ART or after a documented HIV-1 RNA viral load \< 50 copies/ml
• Documented HIV-2 infection
• Using any concomitant therapy disallowed as per the reference safety information and product labeling for the study drugs
• Has AST and/or ALT at least 5-times greater than the upper limit of normal
• Has a creatinine clearance (CrCl) below 50 ml/min (as estimated using the Cockcroft-Gault estimate for glomerular filtration rate)
• Documented opportunistic infection within 4 weeks prior to the study enrolment
• Investigator opinion that the patient should switch or discontinue any ARV in their current regimen immediately for clinical reasons (e.g. anemia with Hb \< 9.5 g/dl while currently on azathioprine (AZT); HBsAg positive without currently being on TDF or TAF plus 3TC or FTC; experiencing adverse events associated with any ARV in current regimen deemed significant enough to warrant immediate change in regimen)
• Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the study
• History or presence of allergy to the study drugs or their components
• BMD monitoring population will also exclude any participant with a pre-existing condition which is likely to decrease validity of bone mineral density estimations (including pre-existing vertebral or bilateral hip fractures, lytic or blastic metastases, bilateral hip arthroplasty, or lumbar spine internal fixation)

Sponsors & Collaborators

• University of Nairobi: lead
• Gilead Sciences: collaborator

Study Sites (2)

Jaramogi Oginga Odinga Teaching and Referral Hospital

Kisumu, Kenya

Location

Kenyatta National Hospital

Nairobi, Kenya

Location

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Study Officials

• Loice Achieng Ombajo, MD, MSc

  University of Nairobi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomised, controlled open-label clinical trial

Study Record Dates

• First Submitted: January 31, 2022
• First Posted: February 17, 2022
• Study Start: February 1, 2022
• Primary Completion: April 11, 2023
• Study Completion: March 18, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 6 months after publication of the final manuscript and for a period of 36 months
• Access Criteria: Access to IPD will be subject to the University of Nairobi data sharing requirements. Written requests should be submitted to the Principal Investigator providing a brief description of the individual or group making the request and detailing the reason for the same. Prior to sharing the data, the requestor will be required to sign a data access and sharing agreement.

Locations

KE (2)