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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: RTV
* Drug: ATV
* Drug: DRV
* Drug: COBI
* Drug: ATV/co
* Drug: DRV/co
* Drug: FTC/TDF
* Drug: ABC/3TC
* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B/F/TAF<br>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<br>* 50/200/25 mg FDC tablet administered orally once daily without regard to food<br>* Other names: Biktarvy®;|
| Experimental: Stay on Baseline Regimen (SBR)<br>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: RTV<br>* 100 mg capsule coadministered orally with ATV or DRV once daily with food<br>Drug: ATV<br>* 300 mg capsule administered orally once daily with food<br>Drug: DRV<br>* 800 mg tablet administered orally once daily with food<br>Drug: COBI<br>* 150 mg tablet coadministered orally with ATV or DRV once daily with food<br>* Other names: GS-9350;Drug: ATV/co<br>* 300/150 mg FDC tablet administered orally once daily with food<br>* Other names: Evotaz®;Drug: DRV/co<br>* 800/150 mg FDC tablet administered orally once daily with food<br>* Other names: Prezcobix®;Drug: FTC/TDF<br>* 200/300 mg FDC tablet administered orally once daily without regard to food<br>* Other names: Truvada®;Drug: ABC/3TC<br>* 600/300 mg tablet administered orally once daily with or without regard to food<br>Drug: B/F/TAF<br>* 50/200/25 mg FDC tablet administered orally once daily without regard to food<br>* Other names: Biktarvy®;|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Change From Baseline in CD4 Cell Count at Week 48 |  | Baseline to Week 48 |