Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: RTV; Drug: ATV; Drug: DRV; Drug: COBI; Drug: ATV/co; Drug: DRV/co; Drug: FTC/TDF; Drug: ABC/3TC

• Study Type: Interventional
• Enrollment (Actual): 578
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
    • Sydney, New South Wales, Australia, 2010
  • Victoria
    • Fitzroy, Victoria, Australia, 3068
    • Melbourne, Victoria, Australia, 3004
    • Prahran, Victoria, Australia, 3141
• Belgium
  • Brussels, Belgium, 1000
  • Ghent, Belgium, 9000
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2T1
  • Ontario
    • Toronto, Ontario, Canada, M5G 1K2
    • Toronto, Ontario, Canada, M5G2N2
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
    • Montreal, Quebec, Canada, H2l 4P9
    • Montreal, Quebec, Canada, H3A 1T1
• Dominican Republic
  • Santo Domingo, Dominican Republic
• France
  • Lyon, France, 69317
  • Nantes, France, 44093
  • Nice, France, 6202
  • Paris, France, 75010
  • Paris, France, 75571
  • Tourcoing, France, 59200
  • Tours, France, 37000
• Germany
  • Berlin, Germany, 13353
  • Berlin, Germany, 12157
  • Bonn, Germany, 53127
  • Essen, Germany, 45122
  • Frankfurt, Germany, 60590
  • Frankfurt, Germany, 60596
  • Hamburg, Germany, 20251
  • Köln, Germany, 50924
  • Munchen, Germany, 81675
  • München, Germany, 80335
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40237
• Italy
  • Milano, Italy, 20157
  • Milano, Italy, 20127
  • Roma, Italy, 00149
• Puerto Rico
  • Ponce, Puerto Rico, 00731
  • Rio Piedras, Puerto Rico, 935
  • San Juan, Puerto Rico, 00935
  • San Juan, Puerto Rico, 00909
• Spain
  • Madrid, Spain, 28040
  • Madrid, Spain, 28034
  • Málaga, Spain, 29010
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
  • Birmingham, United Kingdom, B4 6DH
  • Brighton, United Kingdom, BN2 3EW
  • Edinburgh, United Kingdom, EH4 2XU
  • Liverpool, United Kingdom, L7 8XP
  • London, United Kingdom, SE1 7EH
  • London, United Kingdom, W2 1NY
  • London, United Kingdom, NW3 2QG
  • London, United Kingdom, E1 1BB
  • London, United Kingdom, SW17 0QT
  • London, United Kingdom, SE5 9RJ
  • London, United Kingdom, SW10 9TH
  • Manchester, United Kingdom, M8 5RB
  • Manchester, United Kingdom, M13 0FH
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
    • Phoenix, Arizona, United States, 85015
  • California
    • Los Angeles, California, United States, 90027
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90069
    • Newport Beach, California, United States, 92663
    • Oakland, California, United States, 94602
    • Sacramento, California, United States, 95825
    • San Diego, California, United States, 92103
    • San Francisco, California, United States, 94102
    • San Leandro, California, United States, 94577
    • Torrance, California, United States, 90502
  • Colorado
    • Aurora, Colorado, United States, 80045
  • District of Columbia
    • Washington, District of Columbia, United States, 20017
    • Washington, District of Columbia, United States, 20036
  • Florida
    • DeLand, Florida, United States, 32720
    • Fort Lauderdale, Florida, United States, 33316
    • Fort Pierce, Florida, United States, 34982
    • Miami, Florida, United States, 33136
    • Miami, Florida, United States, 33133
    • Orlando, Florida, United States, 32803-1851
    • Pensacola, Florida, United States, 32504
    • Tampa, Florida, United States, 33614
    • Vero Beach, Florida, United States, 32960
    • West Palm Beach, Florida, United States, 33401
    • Wilton Manors, Florida, United States, 33305
  • Georgia
    • Atlanta, Georgia, United States, 30312
    • Augusta, Georgia, United States, 30912
    • Macon, Georgia, United States, 31201
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
  • Illinois
    • Chicago, Illinois, United States
    • Chicago, Illinois, United States, 60613
    • Chicago, Illinois, United States, 60657
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Massachusetts
    • Boston, Massachusetts, United States, 01211
    • Springfield, Massachusetts, United States, 1105
  • Michigan
    • Berkley, Michigan, United States, 48072
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
  • Missouri
    • Kansas City, Missouri, United States, 64111
    • Saint Louis, Missouri, United States, 63139
  • New York
    • Bronx, New York, United States
    • Bronx, New York, United States, 10467
    • Buffalo, New York, United States, 14215
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7080
    • Charlotte, North Carolina, United States, 28209
    • Durham, North Carolina, United States, 27710
    • Greenville, North Carolina, United States, 27834
    • Huntersville, North Carolina, United States, 28078
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
  • South Carolina
    • Columbia, South Carolina, United States, 29203
  • Tennessee
    • Memphis, Tennessee, United States, 38105
  • Texas
    • Austin, Texas, United States, 78705
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75219
    • Dallas, Texas, United States, 75215
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77098
    • Longview, Texas, United States, 75605
  • Virginia
    • Annandale, Virginia, United States, 22003-7313
  • Washington
    • Seattle, Washington, United States, 98104
    • Spokane, Washington, United States, 99204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit

• Adequate renal function:

  • Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
• Life expectancy ≥ 1 year
• Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
• Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
• No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)

Key Exclusion Criteria:

• An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
• Individuals experiencing decompensated cirrhosis (eg, 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)
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
• A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
• Active, serious infections (other than HIV 1 infection) requiring parenteral 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 individual unsuitable for the study or unable to comply with the dosing requirements
• Any known allergies to the excipients of B/F/TAF FDC or ATV, RTV, DRV, COBI, FTC/TDF or ABC/3TC
• Females who are pregnant (as confirmed by positive serum pregnancy test)
• Females who are breastfeeding
• Acute hepatitis in the 30 days prior to study entry

• Chronic hepatitis B infection in individuals not on a TDF containing regimen, as determined by either:

  • Positive hepatitis B virus (HBV) surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit
  • Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit
• 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 Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B/F/TAF; Randomized Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks, without regard to food. Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks or until the product becomes accessible to participants through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.	Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily without regard to food; Other Names: Biktarvy®
Experimental: Stay on Baseline Regimen (SBR); Randomized Phase: Participants remained on current antiretroviral (ARV) regimen consisting of ritonavir (RTV)-boosted or cobicistat (COBI)-boosted atazanavir (ATV) or darunavir (DRV), plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) for at least 48 weeks with food. Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks or until the product becomes accessible to participants through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.	Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily without regard to food; Other Names: Biktarvy®; Drug: RTV; 100 mg capsule coadministered orally with ATV or DRV once daily with food; Drug: ATV; 300 mg capsule administered orally once daily with food; Drug: DRV; 800 mg tablet administered orally once daily with food; Drug: COBI; 150 mg tablet coadministered orally with ATV or DRV once daily with food; Other Names: Tybost®; GS-9350; Drug: ATV/co; 300/150 mg FDC tablet administered orally once daily with food; Other Names: Evotaz®; Drug: DRV/co; 800/150 mg FDC tablet administered orally once daily with food; Other Names: Prezcobix®; Drug: FTC/TDF; 200/300 mg FDC tablet administered orally once daily without regard to food; Other Names: Truvada®; Drug: ABC/3TC; 600/300 mg tablet administered orally once daily with or without regard to food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines 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 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4 Cell Count at Week 48		Baseline to Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines 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 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Andreatta K, Willkom M, Martin R, Chang S, Wei L, Liu H, Liu YP, Graham H, Quirk E, Martin H, White KL. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. J Antimicrob Chemother. 2019 Dec 1;74(12):3555-3564. doi: 10.1093/jac/dkz347. Erratum In: J Antimicrob Chemother. 2019 Dec 1;74(12):3646-3647.
• Daar ES, DeJesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, Rockstroh JK, Molina JM, Koenig E, Liu YP, Custodio J, Andreatta K, Graham H, Cheng A, Martin H, Quirk E. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018 Jul;5(7):e347-e356. doi: 10.1016/S2352-3018(18)30091-2. Epub 2018 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2015
• Primary Completion (Actual): May 15, 2017
• Study Completion (Actual): December 23, 2019

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cobicistat mixture with darunavir
• Other Study ID Numbers: GS-US-380-1878; 2015-004011-20 (EudraCT Number)

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; Statistical Analysis Plan (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