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

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02603107
• Collaborator: (none)
• Enrollment: 578
• Locations: 119
• Arms: 2
• Actual Duration (Months): 49.1
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

• Study Type: Interventional
• 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: Nov 20, 2015
• Actual Primary Completion Date: May 15, 2017
• Actual Study Completion Date: Dec 23, 2019

Arms and Interventions

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: 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; Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily without regard to food; Other Names: Biktarvy®

Outcome Measures

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 [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 [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 [Baseline to Week 48]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85012
2		Phoenix	Arizona	United States	85015
3		Los Angeles	California	United States	90027
4		Los Angeles	California	United States	90036
5		Los Angeles	California	United States	90069
6		Newport Beach	California	United States	92663
7		Oakland	California	United States	94602
8		Sacramento	California	United States	95825
9		San Diego	California	United States	92103
10		San Francisco	California	United States	94102
11		San Leandro	California	United States	94577
12		Torrance	California	United States	90502
13		Aurora	Colorado	United States	80045
14		Washington	District of Columbia	United States	20017
15		Washington	District of Columbia	United States	20036
16		DeLand	Florida	United States	32720
17		Fort Lauderdale	Florida	United States	33316
18		Fort Pierce	Florida	United States	34982
19		Miami	Florida	United States	33133
20		Miami	Florida	United States	33136
21		Orlando	Florida	United States	32803-1851
22		Pensacola	Florida	United States	32504
23		Tampa	Florida	United States	33614
24		Vero Beach	Florida	United States	32960
25		West Palm Beach	Florida	United States	33401
26		Wilton Manors	Florida	United States	33305
27		Atlanta	Georgia	United States	30312
28		Augusta	Georgia	United States	30912
29		Macon	Georgia	United States	31201
30		Honolulu	Hawaii	United States	96813
31		Chicago	Illinois	United States	60613
32		Chicago	Illinois	United States	60657
33		Chicago	Illinois	United States
34		Kansas City	Kansas	United States	66160
35		Louisville	Kentucky	United States	40202
36		New Orleans	Louisiana	United States	70112
37		Boston	Massachusetts	United States	01211
38		Springfield	Massachusetts	United States	1105
39		Berkley	Michigan	United States	48072
40		Minneapolis	Minnesota	United States	55407
41		Kansas City	Missouri	United States	64111
42		Saint Louis	Missouri	United States	63139
43		Bronx	New York	United States	10467
44		Bronx	New York	United States
45		Buffalo	New York	United States	14215
46		Chapel Hill	North Carolina	United States	27599-7080
47		Charlotte	North Carolina	United States	28209
48		Durham	North Carolina	United States	27710
49		Greenville	North Carolina	United States	27834
50		Huntersville	North Carolina	United States	28078
51		Philadelphia	Pennsylvania	United States	19107
52		Columbia	South Carolina	United States	29203
53		Memphis	Tennessee	United States	38105
54		Austin	Texas	United States	78705
55		Dallas	Texas	United States	75215
56		Dallas	Texas	United States	75219
57		Dallas	Texas	United States	75246
58		Houston	Texas	United States	77004
59		Houston	Texas	United States	77098
60		Longview	Texas	United States	75605
61		Annandale	Virginia	United States	22003-7313
62		Seattle	Washington	United States	98104
63		Spokane	Washington	United States	99204
64		Darlinghurst	New South Wales	Australia	2010
65		Sydney	New South Wales	Australia	2010
66		Fitzroy	Victoria	Australia	3068
67		Melbourne	Victoria	Australia	3004
68		Prahran	Victoria	Australia	3141
69		Brussels		Belgium	1000
70		Ghent		Belgium	9000
71		Vancouver	British Columbia	Canada	V6Z 2T1
72		Toronto	Ontario	Canada	M5G 1K2
73		Toronto	Ontario	Canada	M5G2N2
74		Montreal	Quebec	Canada	H2L 4P9
75		Montreal	Quebec	Canada	H3A 1T1
76		Montreal	Quebec	Canada	H4A 3J1
77		Santo Domingo		Dominican Republic
78		Lyon		France	69317
79		Nantes		France	44093
80		Nice		France	6202
81		Paris		France	75010
82		Paris		France	75571
83		Tourcoing		France	59200
84		Tours		France	37000
85		Düsseldorf	Nordrhein-Westfalen	Germany	40237
86		Berlin		Germany	12157
87		Berlin		Germany	13353
88		Bonn		Germany	53127
89		Essen		Germany	45122
90		Frankfurt		Germany	60590
91		Frankfurt		Germany	60596
92		Hamburg		Germany	20251
93		Köln		Germany	50924
94		Munchen		Germany	81675
95		München		Germany	80335
96		Milano		Italy	20127
97		Milano		Italy	20157
98		Roma		Italy	00149
99		Ponce		Puerto Rico	00731
100		Rio Piedras		Puerto Rico	935
101		San Juan		Puerto Rico	00909
102		San Juan		Puerto Rico	00935
103		Madrid		Spain	28034
104		Madrid		Spain	28040
105		Málaga		Spain	29010
106		Birmingham		United Kingdom	B4 6DH
107		Birmingham		United Kingdom	B9 5SS
108		Brighton		United Kingdom	BN2 3EW
109		Edinburgh		United Kingdom	EH4 2XU
110		Liverpool		United Kingdom	L7 8XP
111		London		United Kingdom	E1 1BB
112		London		United Kingdom	NW3 2QG
113		London		United Kingdom	SE1 7EH
114		London		United Kingdom	SE5 9RJ
115		London		United Kingdom	SW10 9TH
116		London		United Kingdom	SW17 0QT
117		London		United Kingdom	W2 1NY
118		Manchester		United Kingdom	M13 0FH
119		Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol: Original - Oct 21, 2015
• Study Protocol: Amendment 1 - Feb 19, 2016
• Study Protocol: Amendment 2 - Oct 19, 2016
• Statistical Analysis Plan: Week 48 - May 16, 2017
• Statistical Analysis Plan: Final - Apr 24, 2020

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02603107
• Other Study ID Numbers: GS-US-380-1878; 2015-004011-20
• First Posted: Nov 11, 2015
• Last Update Posted: Dec 29, 2020
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cobicistat mixture with darunavir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Dominican Republic, North America, Australia, and Europe. The first participant was screened on 20 November 2015. The last study visit occurred on 23 December 2019.
Pre-assignment Detail	707 participants were screened.

Arm/Group Title	B/F/TAF	Stay on Baseline Regimen (SBR)
Arm/Group Description	Randomized Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed-dose combination (FDC) tablet orally once daily for at least 48 weeks, without regard to food. Extension Phase: After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first.	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) (200/300 mg) FDC tablet or abacavir/lamivudine (ABC/3TC) (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food. Extension Phase: After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first.
Period Title: Randomized Phase
STARTED	290	287
COMPLETED	275	266
NOT COMPLETED	15	21
Period Title: Randomized Phase
STARTED	272	245
COMPLETED	263	232
NOT COMPLETED	9	13

Baseline Characteristics

Arm/Group Title	B/F/TAF	Stay on Baseline Regimen (SBR)	Total
Arm/Group Description	Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food. Extension Phase: After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first.	Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablets or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food. Extension Phase: After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first.	Total of all reporting groups
Overall Participants	290	287	577
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (10.5)	46 (10.5)	46 (10.5)
Sex: Female, Male (Count of Participants)
Female	47 16.2%	53 18.5%	100 17.3%
Male	243 83.8%	234 81.5%	477 82.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	3 1%	3 1%	6 1%
Asian	6 2.1%	10 3.5%	16 2.8%
Black	79 27.2%	72 25.1%	151 26.2%
Native Hawaiian or Pacific Islander	0 0%	0 0%	0 0%
White	188 64.8%	190 66.2%	378 65.5%
Other	14 4.8%	12 4.2%	26 4.5%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	60 20.7%	47 16.4%	107 18.5%
Not Hispanic or Latino	230 79.3%	240 83.6%	470 81.5%
Region of Enrollment (Count of Participants)
Australia	15 5.2%	16 5.6%	31 5.4%
Canada	18 6.2%	15 5.2%	33 5.7%
Belgium	2 0.7%	3 1%	5 0.9%
France	17 5.9%	17 5.9%	34 5.9%
Germany	28 9.7%	33 11.5%	61 10.6%
Italy	3 1%	5 1.7%	8 1.4%
Spain	6 2.1%	4 1.4%	10 1.7%
United Kingdom	31 10.7%	23 8%	54 9.4%
United States	166 57.2%	164 57.1%	330 57.2%
Dominican Republic	4 1.4%	7 2.4%	11 1.9%
HIV-1 RNA Category (Count of Participants)
< 50 copies/mL	285 98.3%	277 96.5%	562 97.4%
≥ 50 copies/mL	5 1.7%	10 3.5%	15 2.6%
CD4 Cell Count (cells/μL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/μL]	669 (303.4)	657 (285.0)	663 (294.2)
CD4 Cell Count Category (Count of Participants)
< 50 cells/μL	0 0%	0 0%	0 0%
≥ 50 to < 200 cells/μL	4 1.4%	8 2.8%	12 2.1%
≥ 200 to < 350 cells/μL	26 9%	30 10.5%	56 9.7%
≥ 350 to < 500 cells/μL	62 21.4%	60 20.9%	122 21.1%
≥ 500 cells/μL	198 68.3%	189 65.9%	387 67.1%
HIV Disease Status (Count of Participants)
Asymptomatic	240 82.8%	234 81.5%	474 82.1%
Symptomatic HIV Infection	16 5.5%	20 7%	36 6.2%
Acquired Immunodeficiency Syndrome (AIDS)	34 11.7%	33 11.5%	67 11.6%
Prior ARV Regimen (Count of Participants)
Boosted ATV + ABC/3TC	21 7.2%	23 8%	44 7.6%
Boosted DRV + ABC/3TC	24 8.3%	21 7.3%	45 7.8%
Boosted ATV + FTC/TDF	105 36.2%	110 38.3%	215 37.3%
Boosted DRV + FTC/TDF	140 48.3%	133 46.3%	273 47.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all participants who were randomized into the study and received at least 1 dose of study drug.

Arm/Group Title	B/F/TAF	Stay on Baseline Regimen (SBR)
Arm/Group Description	Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.	Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.
Measure Participants	290	287
Number [percentage of participants]	1.7 0.6%	1.7 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	B/F/TAF, Stay on Baseline Regimen (SBR)
	Comments	The null hypothesis was that the percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 in the B/F/TAF group was at least 4% higher than the rate in the SBR group; the alternative hypothesis was that the percentage of participants with HIV-1 RNA ≥ 50 copies/mL in the B/F/TAF group was less than 4% higher than that in the SBR group.
	Type of Statistical Test	Non-Inferiority
	Comments	A sample size of 520 participants (260 participants per treatment group) would provide at least 90% power to establish a non-inferiority margin of 4% in the Week 48 response rate (HIV-1 RNA ≥ 50 copies/mL) between the 2 treatment groups. Sample size was based on the assumptions that both treatment groups have 2% of participants with HIV-1 RNA ≥ 50 copies/mL (based on Gilead Genvoya and Stribild studies) and that the significance level of the test is at a 1-sided 0.025 level.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95.002%; -2.5 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in percentages and its 95.002% confidence interval (CI) were calculated based on an unconditional exact method using 2 inverted 1-sided tests.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B/F/TAF, Stay on Baseline Regimen (SBR)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
Description	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.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	B/F/TAF	Stay on Baseline Regimen (SBR)
Arm/Group Description	Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.	Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.
Measure Participants	290	287
Number [percentage of participants]	92.1 31.8%	88.9 31%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	B/F/TAF, Stay on Baseline Regimen (SBR)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority of B/F/TAF would be established if the lower bound of the 2-sided 95.002% CI of the difference between the treatment groups (B/F/TAF group - SBR group) in the percentage of participants with HIV-1 RNA < 50 copies/mL is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95.002%; -1.6 to 8.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in percentages and its 95.002% confidence interval (CI) were calculated based on an unconditional exact method using 2 inverted 1-sided tests.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B/F/TAF, Stay on Baseline Regimen (SBR)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change From Baseline in CD4 Cell Count at Week 48
Time Frame	Baseline to Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	B/F/TAF	Stay on Baseline Regimen (SBR)
Arm/Group Description	Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.	Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.
Measure Participants	265	256
Mean (Standard Deviation) [cells/μL]	25 (151.2)	0 (159.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	B/F/TAF, Stay on Baseline Regimen (SBR)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means (LSM)
	Estimated Value	25
	Confidence Interval	(2-Sided) 95%; -2 to 52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From the first dose date up to last dose date (maximum: 181 weeks) plus 30 days
Adverse Event Reporting Description	Safety Analysis Set included participants who were randomized into the study and received at least 1 dose of study drug.
Arm/Group Title	B/F/TAF (Randomized Phase)		Stay on Baseline Regimen (SBR) (Randomized Phase)		Extension B/F/TAF From B/F/TAF		Extension B/F/TAF From SBR
Arm/Group Description	Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.		Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.		After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first.		After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first.
All Cause Mortality
	B/F/TAF (Randomized Phase)		Stay on Baseline Regimen (SBR) (Randomized Phase)		Extension B/F/TAF From B/F/TAF		Extension B/F/TAF From SBR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/290 (0.3%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Serious Adverse Events
	B/F/TAF (Randomized Phase)		Stay on Baseline Regimen (SBR) (Randomized Phase)		Extension B/F/TAF From B/F/TAF		Extension B/F/TAF From SBR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/290 (5.9%)		21/287 (7.3%)		20/272 (7.4%)		29/244 (11.9%)
Blood and lymphatic system disorders
Lymphadenitis	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Cardiac disorders
Acute myocardial infarction	1/290 (0.3%)		1/287 (0.3%)		1/272 (0.4%)		0/244 (0%)
Atrial fibrillation	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Bradycardia	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Coronary artery stenosis	1/290 (0.3%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Myocardial infarction	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Myocardial ischaemia	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Myxomatous mitral valve degeneration	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Sinus node dysfunction	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Eye disorders
Optic disc disorder	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Gastrointestinal disorders
Abdominal pain	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Anal fistula	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Diarrhoea	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Diverticular perforation	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Enterocutaneous fistula	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Lower gastrointestinal haemorrhage	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Small intestinal obstruction	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
General disorders
Chest pain	1/290 (0.3%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Oedema peripheral	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Hepatobiliary disorders
Biliary dyskinesia	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Cholelithiasis	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Infections and infestations
Abscess limb	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Acute hepatitis C	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Anal abscess	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Appendicitis	0/290 (0%)		1/287 (0.3%)		1/272 (0.4%)		1/244 (0.4%)
Bronchitis	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Cellulitis	1/290 (0.3%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Diverticulitis	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Erysipelas	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		1/244 (0.4%)
Hepatitis A	2/290 (0.7%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Hepatitis C	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Infection	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Influenza	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Localised infection	0/290 (0%)		1/287 (0.3%)		1/272 (0.4%)		0/244 (0%)
Neurosyphilis	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Osteomyelitis	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Osteomyelitis chronic	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Pneumonia	1/290 (0.3%)		0/287 (0%)		1/272 (0.4%)		1/244 (0.4%)
Pyelonephritis	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Pyelonephritis acute	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Stoma site abscess	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Upper respiratory tract infection	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Urinary tract infection	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Urinary tract infection bacterial	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Injury, poisoning and procedural complications
Accident	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Acetabulum fracture	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Head injury	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Humerus fracture	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Joint dislocation	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Radius fracture	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Skin laceration	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Tibia fracture	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		1/244 (0.4%)
Upper limb fracture	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Osteoarthritis	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Bladder neoplasm	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Brain cancer metastatic	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Lung neoplasm malignant	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Uterine leiomyoma	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Nervous system disorders
Carotid artery stenosis	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Cerebral infarction	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Cervical radiculopathy	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Metabolic encephalopathy	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Thrombotic stroke	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/290 (0%)		0/287 (0%)		0/272 (0%)		2/244 (0.8%)
Foetal death	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Psychiatric disorders
Alcohol abuse	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Alcoholism	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Anxiety	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Mania	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Schizoaffective disorder	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Schizophrenia	1/290 (0.3%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Suicidal ideation	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Suicide attempt	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Renal and urinary disorders
Acute kidney injury	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Ureteric stenosis	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		1/244 (0.4%)
Ureterolithiasis	1/290 (0.3%)		0/287 (0%)		0/272 (0%)		0/244 (0%)
Reproductive system and breast disorders
Pelvic haematoma	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Priapism	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Asthma	1/290 (0.3%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Dyspnoea	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Sleep apnoea syndrome	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Social circumstances
Physical assault	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Surgical and medical procedures
Hip arthroplasty	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Vascular disorders
Deep vein thrombosis	0/290 (0%)		0/287 (0%)		0/272 (0%)		1/244 (0.4%)
Hypertensive crisis	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Hypotension	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Hypovolaemic shock	0/290 (0%)		1/287 (0.3%)		0/272 (0%)		0/244 (0%)
Peripheral artery stenosis	0/290 (0%)		0/287 (0%)		1/272 (0.4%)		0/244 (0%)
Other (Not Including Serious) Adverse Events
	B/F/TAF (Randomized Phase)		Stay on Baseline Regimen (SBR) (Randomized Phase)		Extension B/F/TAF From B/F/TAF		Extension B/F/TAF From SBR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/290 (40.3%)		126/287 (43.9%)		108/272 (39.7%)		113/244 (46.3%)
Gastrointestinal disorders
Diarrhoea	24/290 (8.3%)		17/287 (5.9%)		19/272 (7%)		12/244 (4.9%)
Infections and infestations
Influenza	7/290 (2.4%)		12/287 (4.2%)		10/272 (3.7%)		15/244 (6.1%)
Nasopharyngitis	23/290 (7.9%)		35/287 (12.2%)		24/272 (8.8%)		38/244 (15.6%)
Syphilis	9/290 (3.1%)		11/287 (3.8%)		14/272 (5.1%)		14/244 (5.7%)
Upper respiratory tract infection	23/290 (7.9%)		24/287 (8.4%)		24/272 (8.8%)		27/244 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/290 (5.2%)		16/287 (5.6%)		12/272 (4.4%)		9/244 (3.7%)
Back pain	13/290 (4.5%)		19/287 (6.6%)		15/272 (5.5%)		13/244 (5.3%)
Nervous system disorders
Headache	34/290 (11.7%)		14/287 (4.9%)		13/272 (4.8%)		17/244 (7%)
Respiratory, thoracic and mediastinal disorders
Cough	12/290 (4.1%)		9/287 (3.1%)		14/272 (5.1%)		8/244 (3.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years