Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants (BRAAVE 2020)

A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants

The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)Ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed African American participants.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: NRTIs; Drug: Third Agent

• Study Type: Interventional
• Enrollment (Actual): 496
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36608
      • Alabama Medical Group, PC
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc.
    • Oakland, California, United States, 94611
      • Kaiser Permanente
    • Oakland, California, United States, 94602
      • Highland Hospital- Alameda Health System
    • Sacramento, California, United States, 95811
      • One Community Health
    • Sacramento, California, United States, 95825
      • Kaiser Permanente
    • San Leandro, California, United States, 94577
      • Kaiser Permanente, Department of Infectious Diseases
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
    • Washington, District of Columbia, United States, 20017
      • Washington Health Institute
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
    • Washington, District of Columbia, United States, 20037
      • The GW Medical Faculty Associates
    • Washington, District of Columbia, United States, 20005
      • Whitman-Walker Health
  • Florida
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond, M.D., P.A.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33133
      • AHF- The Kinder Medical Group
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine Division of Infectious Disease
    • Miami Beach, Florida, United States, 33140
      • AIDS Healthcare Foundation - South Beach
    • Orlando, Florida, United States, 32803-1851
      • Orlando Immunology Center
    • Tampa, Florida, United States, 33614
      • St. Joseph's Hospital Comprehensive Research Institute
    • Vero Beach, Florida, United States, 32960
      • AIDS Research & Treatment Center of the Treasure Coast
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group, PC
    • Atlanta, Georgia, United States, 30308
      • Emory Hospital Midtown Infectious Disease Clinic
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialist of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University, Department of Internal Medicine
    • Savannah, Georgia, United States, 31401
      • Chatham County Health Department
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46077
      • Indiana CTSI Clinical Research Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center- New Orleans (UMCNO)
    • New Orleans, Louisiana, United States, 70119
      • SLVHCS Building J, 7th floor, Outpatient Infectious Disease Clinic
    • New Orleans, Louisiana, United States, 70130
      • CrescentCare Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
    • Springfield, Massachusetts, United States, 01105
      • Claudia T. Martorell, MD, LLC d/b/a The Research Institute
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University- Integrative Bioscience Center
    • Southfield, Michigan, United States, 48075
      • St. John Newland Medical Associates
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Hennepin County Medical Center, Positive Care Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • G.V. 'Sonny' Montgomery VAMC
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
    • Saint Louis, Missouri, United States, 63108
      • Southampton Clinical Research
    • Saint Louis, Missouri, United States, 63110
      • Clinical: Saint Louis University, New Hope Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Huntridge Family Clinic
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Prime Healthcare Services- St. Michael's LLC d/b/a Saint Michael's Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital/Division of Infectious Diseases
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28207
      • UT Physicians
    • Durham, North Carolina, United States, 27710
      • Duke University Health System
    • Greenville, North Carolina, United States, 27834
      • East Carolina University, The Brody School of Medicine, ECU Adult Specialty Care
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
    • Pensacola, North Carolina, United States, 32504
      • AHF
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT Community Health Centers
    • Philadelphia, Pennsylvania, United States, 19066
      • Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health Richland
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Bellaire, Texas, United States, 77401
      • St. Hope Foundation
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, P.A.
    • Dallas, Texas, United States, 75208
      • AIDS Arms, Inc. DBA Prism Health North Texas
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)
    • Houston, Texas, United States, 77030
      • Thomas Street Health Center
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Washington
    • Tacoma, Washington, United States, 98405
      • Community Health Care, Hilltop Medical Clinic
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Self-describes as Black, African American, or mixed race, including Black
• Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months
• Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc
• If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded
• Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI)
• Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen)
• History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded
• Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit
• HIV-1 RNA levels < 50 copies/mL at Screening
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance

Key Exclusion Criteria:

• History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT
• No desire to switch from current ARVs
• An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
• Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
• Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). A prior malignancy treated with curative therapy and for which there has been no evidence of disease for at least five years prior to screening is allowed
• Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance
• Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal therapy within 30 days prior to Day 1
• Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements
• Known hypersensitivity to FDC of B/F/TAF tablets, their metabolites, or formulation excipient
• Females who are pregnant (as confirmed by positive serum pregnancy test)
• Females who are breastfeeding
• Acute hepatitis in the 30 days prior to randomization
• Active tuberculosis infection.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: B/F/TAF; Participants will receive B/F/TAF (50/200/25 mg) FDC tablet orally once daily for 48 weeks, without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.	Drug: B/F/TAF; 50/200/25 mg FDC tablets administered orally once daily without regard to food; Other Names: Biktarvy®
ACTIVE_COMPARATOR: Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF; Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.	Drug: B/F/TAF; 50/200/25 mg FDC tablets administered orally once daily without regard to food; Other Names: Biktarvy®; Drug: NRTIs; The following NRTIs will be administered as prescribed until Week 24 without regard to food: abacavir (ABC), emtricitabine (FTC), lamivudine (3TC), tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), zidovudine (ZDV or AZT); Drug: Third Agent; Any one of the following third agents will be administered as prescribed. Protease inhibitors and EVG will be administered with the appropriate pharmacologic booster cobicistat or ritonavir. : Non-nucleoside reverse transcriptase inhibitors (NNRTIs)delavirdine (DLV)efavirenz (EFV)nevirapine (NVP)rilpivirine (RPV)doravirine (DOR); Integrase inhibitorsdolutegravir (DTG)elvitegravir (EVG)raltegravir (RAL); Protease inhibitors (PIs)atazanavir (ATV)darunavir (DRV)lopinavir (LPV)nelfinavir NFV)saquinavir (SQV)tipranavir (TPV); Chemokine co-recptor 5 (CCR5) antagonist --maraviroc (MVC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set	The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set	The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.	Week 48
Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set	The percentage of participants who had HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 24
Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Week 24 Per Protocol Analysis Set	The percentage of participants who had HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 24
Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set	The percentage of participants who had HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.	Week 48
Change From Baseline in CD4+ Cell Count at Week 24: Full Analysis Set	The analysis includes values up to 1 day after permanent discontinuation of study treatment.	Baseline to Week 24
Change From Baseline in CD4+ Cell Count at Week 24: Week 24 Per Protocol Analysis Set	The analysis includes values up to 1 day after permanent discontinuation of study treatment.	Baseline to Week 24
Change From Baseline in CD4+ Cell Count at Week 48: Full Analysis Set	The analysis includes values up to 1 day after permanent discontinuation of study treatment. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.	Baseline to Week 48
Percentage of Participants Experiencing Treatment-Emergent Adverse Events	An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product, which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A treatment-emergent adverse event was defined as any adverse event with onset date on or after the study treatment start date and no later than 30 days after the study drug stop date; or any adverse event leading to study drug discontinuation.	First B/F/TAF dose date up to Week 72 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Severity grades were defined by 'Gilead Grading Scale for Severity of AEs and Laboratory Abnormalities'.	First B/F/TAF dose date up to Week 72 plus 30 days

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Andreatta K, D'Antoni ML, Chang S, Parvangada A, Martin R, Blair C, et al. Preexisting Resistance and Week 48 Virologic Outcomes after Switching to B/F/TAF in African American Adults With HIV [Presentation]. IDWeek Virtual; 2020b 21-25 October.
• Hagins D, Kumar P, Saag M, Wurapa AK, Brar I, Berger D, Osiyemi O, Hileman CO, Ramgopol M, McDonald C, Blair C, Andreatta K, Collins SE, Brainard D, Martin H. Week-48 Outcomes From the BRAAVE 2020 Study: a Randomized Switch to B/F/TAF in African-American Adults With HIV, IDWeek 2020, October 21-25. Abstract 1046.
• Andreatta K, D'Antoni ML, Chang S, Martin R, Blair C, Collins SE, et al. Preexisting Resistance and B/F/TAF Switch Efficacy in African Americans [Poster 509]. Conference on Retroviruses and Opportunistic Infections (CROI); 2020b 08-11 March; Boston, MA.
• Hagins D, Kumar P, Saag M, Wurapa AK, Brar I, Berger D, Osiyemi O, Hileman CO, Ramgopol M, McDonald C, Blair C, Andreatta K, Collins SE, Brainard D, Martin H. Randomized Switch to B/F/TAF in African American Adults with HIV. Conference on Retroviruses and Opportunistic Infections 2020, March 7-11, Boston MA. Abstract 2979.
• Hagins D, Kumar P, Saag M, Wurapa AK, Brar I, Berger D, Osiyemi O, Hileman CO, Ramgopal MN, McDonald C, Blair C, Andreatta K, Collins SE, Brainard DM, Martin H; BRAAVE2020 Investigators. Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. J Acquir Immune Defic Syndr. 2021 Sep 1;88(1):86-95. doi: 10.1097/QAI.0000000000002731.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 28, 2018
• Primary Completion (ACTUAL): August 12, 2019
• Study Completion (ACTUAL): August 19, 2020

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (ACTUAL): August 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-380-4580

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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