B/F/TAF vs Atripla Double-Blind Switch Study in HIV-1 Infected Adults

Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate to Bictegravir/ Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected Virologically Suppressed Adults

Atripla (ATP: FTC/TDF/EFV) was the first single pill treatment for HIV and was the most prescribed first-line treatment from approximately 2008 to 2013 for people infected with HIV. However, ATP has not been recommended as a "preferred" treatment for HIV since 2015, due to there now being single pill treatments that work better. There are a lot of people who are still taking ATP and it is working for them. However, it has the potential to cause serious side effects (chronic kidney disease and fractures and serious neurological effects). These side effects are caused by components in ATP (namely the TDF and EFV parts). Also, the efavirenz (EFV) component is not compatible for treatment of Hepatitis C (HCV) - which is often also seen in people who have HIV. For these reasons, there is a need to find a better alternative treatment for these people currently being treated with ATP.

Study Overview

• Status: Terminated
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: Atripla Placebo; Drug: Atripla; Drug: B/F/TAF Placebo

Detailed Description

B/F/TAF (bictegravir/FTC/TAF) is an investigational single pill drug treatment drug that contains neither TDF nor EFV. This study is looking at whether changing people to this new drug treatment will continue to suppress their HIV and have fewer side effects.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HIV-1 seropositive
2. Age > 21 years
3. Receiving ATP > 2 years as their only ART, with HIV-1 RNA < 50 copies/mL at screening and all HIV-1 RNA tests < 100 copies/mL in the past 18 months
4. No documented resistance mutations to the components of ATP
5. Any CD4 count, but no active AIDS-defining opportunistic infections or cancers
6. HBsAg+ permitted if plasma HBV DNA is unquantifiable and the patient does not have decompensated liver disease

Exclusion Criteria:

1. Pregnancy, breastfeeding or planned pregnancy in the next 2 years
2. Documented resistance to the components of ATP
3. Active AIDS-defining opportunistic infection or cancer
4. Cancer in past 3 years, except non melanoma skin cancer
5. Active psychotic disease or active depression that may interfere with study participation according investigator discretion
6. Any illness with a life expectancy less than 2 years
7. eGFR < 50 mL/min
8. Urine protein/creatinine > 40 mg/mmoL
9. Patients who the investigator feels are unlikely to commit to the study requirements for any reason
10. Prescription drug therapy for osteoporosis (calcium and/or vitamin D is allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B/F/TAF; B/F/TAF + Atripla Placebo Each pill is taken once daily, (total of 2 tablets) The blinded treatment phase of this study will last for 52 weeks	Drug: B/F/TAF; B/F/TAF (Bictegravir 50mg/ Emtricitabine 200mg/ Tenofovir Alafenamide 25mg) Tablet taken orally once daily; Other Names: BIKTARVY®; Drug: Atripla Placebo; Tablet taken orally once daily
Active Comparator: Atripla; Atripla + B/F/TAF Placebo Each pill is taken once daily, (total of 2 tablets) The blinded treatment phase of this study will last for 52 weeks	Drug: Atripla; Atripla (Efavirenz 600mg/ emtricitabine 200 mg/ tenofovir disoproxil 245 mg) Tablet taken orally once daily; Drug: B/F/TAF Placebo; Tablet taken orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Albumin/Creatinine Ratio (UACR)	change in urine albumin/creatinine ratio (UACR)	Baseline and week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-1 RNA	Number of participants with HIV-1 RNA < 50 copies/mL	Week 48
Efavirenz (EFV) Symptom Scores	change in EFV symptom scores from Pittsburgh Sleep Quality Questionnaire (PSQI) global score. PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. The PSQI global score has a possible range of 0-21. Higher scores represent worse sleep quality.	Baseline and week 4
Urine Protein/Creatinine Ratio (UPCR)	change in urine protein/creatinine ratio (UPCR)	Baseline and week 48
Estimated Glomerular Filtration Rate (eGFR)	change in estimated glomerular filtration rate (eGFR)	Baseline and week 48
Bone Mineral Density (BMD) at the Hip	change in bone mineral density (BMD) at the hip	Baseline and week 48
Bone Mineral Density (BMD) at the Spine	change in bone mineral density (BMD) at the spine	Baseline and week 48
CD4 Lymphocyte Counts	change in CD4 lymphocyte counts	Baseline and week 48
Serum Lipids	change in serum lipids	Baseline and week 48
Adverse Events	number of adverse events	Baseline, week 4, week 12, week 24, week 36, and week 48

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: University of British Columbia; Gilead Sciences
• Investigators: Principal Investigator: Stephen D Shafran, MD, University of Alberta

Publications and helpful links

General Publications

• Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2063-2072. doi: 10.1016/S0140-6736(17)32299-7. Epub 2017 Aug 31.
• Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, Antinori A, Workowski K, Slim J, Reynes J, Garner W, Custodio J, White K, SenGupta D, Cheng A, Quirk E. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2073-2082. doi: 10.1016/S0140-6736(17)32340-1. Epub 2017 Aug 31.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2018
• Primary Completion (Actual): August 3, 2020
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: May 9, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Estimate): December 14, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: BFTAF vs Atripla

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes