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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: RTV; Drug: ATV; Drug: DRV; Drug: COBI; Drug: ATV/co; Drug: DRV/co; Drug: FTC/TDF; Drug: ABC/3TC; Drug: B/F/TAF	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	578 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	November 20, 2015
Actual Primary Completion Date :	May 15, 2017
Estimated Study Completion Date :	July 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: B/F/TAF; Randomized Phase: Participants will switch to B/F/TAF FDC and continue treatment for at least 48 weeks. Extension Phase: After Week 48, participants in countries where B/F/TAF is not available may have the option to receive B/F/TAF for up to 96 additional weeks.	Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily without regard to food; Other Name: Biktarvy®
Experimental: Current antiretroviral regimen; Randomized Phase: Participants will remain on current antiretroviral regimen consisting of ritonavir boosted ATV (RTV+ATV), ritonavir boosted DRV (RTV+DRV), cobicistat boosted ATV (COBI+ATV or ATV/co), or cobicistat boosted DRV (COBI+DRV or DRV/co) plus either FTC/TDF or ABC/3TC for at least 48 weeks. Extension Phase: After Week 48, participants in countries where B/F/TAF is not available may have the option to receive B/F/TAF for up to 96 additional weeks.	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 Name: Evotaz®; Drug: DRV/co; 800/150 mg FDC tablet administered orally once daily with food; Other Name: Prezcobix®; Drug: FTC/TDF; 200/300 mg FDC tablet administered orally once daily without regard to food; Other Name: Truvada®; Drug: ABC/3TC; 600/300 mg tablet administered orally once daily with or without regard to food; Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily without regard to food; Other Name: Biktarvy®

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm [ Time Frame: Week 48 ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm [ Time Frame: Week 48 ]
   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.
2. Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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  Show 119 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:	Gilead Study Director	Gilead Sciences

  Study Documents (Full-Text)

Documents provided by Gilead Sciences:

Study Protocol: Original  [PDF] October 21, 2015

Study Protocol: Amendment 1  [PDF] February 19, 2016

Study Protocol: Amendment 2  [PDF] October 19, 2016

Statistical Analysis Plan  [PDF] May 16, 2017

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT02603107 History of Changes
Other Study ID Numbers:	GS-US-380-1878; 2015-004011-20 ( EudraCT Number )
First Posted:	November 11, 2015
Results First Posted:	June 5, 2018
Last Update Posted:	September 24, 2018
Last Verified:	May 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Tenofovir; Lamivudine; Emtricitabine; Darunavir; Atazanavir Sulfate; Abacavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Antiviral Agents; Anti-Infective Agents	Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Anti-HIV Agents; HIV Protease Inhibitors; Protease Inhibitors