Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02121795
• Collaborator: (none)
• Enrollment: 668
• Locations: 78
• Arms: 2
• Actual Duration (Months): 57.8
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF.

This study will consist of a 96 week double-blind treatment period. After Week 96, all participants will continue on blinded study drug treatment and attend visits every 12 weeks until treatment assignments are unblinded. All participants will return for an unblinding visit and will be given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical development program.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: FTC/TDF; Drug: F/TAF; Drug: Allowed third antiretroviral agent; Drug: FTC/TDF Placebo; Drug: F/TAF Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 668 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF
• Actual Study Start Date: May 6, 2014
• Actual Primary Completion Date: Aug 12, 2015
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: F/TAF + 3rd Agent Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks. Dosing of F/TAF will be dependent on the third agent of the participants' pre-existing treatment regimen.	Drug: F/TAF; Tablets administered orally once daily; Other Names: Descovy® ; Drug: Allowed third antiretroviral agent; An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).; Drug: FTC/TDF Placebo; Tablets administered orally once daily
Active Comparator: FTC/TDF + 3rd Agent Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.	Drug: FTC/TDF; 200/300 mg FDC tablets administered orally once daily; Other Names: Truvada® ; Drug: Allowed third antiretroviral agent; An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).; Drug: F/TAF Placebo; Tablets administered orally once daily

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis [Week 48]

   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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 Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [Baseline; Week 48]

   Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.

2. Percentage Change From Baseline in Spine BMD at Week 48 [Baseline; Week 48]

   Spine BMD was assessed by DXA scan.

3. Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis [Week 48]

   The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

4. Change From Baseline in CD4+ Cell Count at Week 48 [Baseline; Week 48]

5. Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis [Week 96]

   The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

6. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis [Week 96]

   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

7. Percentage Change From Baseline in Hip BMD at Week 96 [Baseline; Week 96]

   Hip BMD was assessed by DXA scan.

8. Percentage Change From Baseline in Spine BMD at Week 96 [Baseline; Week 96]

   Spine BMD was assessed by DXA scan.

9. Change From Baseline in CD4+ Cell Count at Week 96 [Baseline; Week 96]

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures

• Currently receiving antiretroviral regimen containing FTC/TDF in combination with one third agent for ≥ 6 consecutive months prior to screening.

• Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year.

• Plasma HIV-1 RNA should be < 50 copies/mL at the screening visit.

• Normal electrocardiogram (ECG)

• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of the normal range (ULN)

• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 x ULN)

• Adequate hematologic function

• Serum amylase ≤ 5 × ULN

• Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active, or practice abstinence from screening throughout the duration of the study treatment and for 30 days following the last dose of the study drug.

• Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range.

• Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.

• Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening

• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable

• Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)

• Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)

• Females who are breastfeeding

• Positive serum pregnancy test

• Have an implanted defibrillator or pacemaker

• Current alcohol or substance use judged by the investigator to potentially interfere with study compliance

• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit

• Individuals receiving ongoing therapy with any of the medications not to be used with FTC, TAF, TDF or other antiretroviral third agents.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Spectrum Medical Group	Phoenix	Arizona	United States	85012
3	Pacific Oaks Medical Group	Beverly Hills	California	United States	90211
4	Kaiser Permanente	Hayward	California	United States	94545
5	Tarrant County ID Associates	Los Angeles	California	United States	90036
6	Southern California Men's Medical Group	Los Angeles	California	United States	90069
7	Highland Hospital - Alameda Health System (formerly Alameda County medical Center)	Oakland	California	United States	94602
8	Kaiser Permanente Sacramento Medical Center	Sacramento	California	United States	95825
9	La Playa Medical Group and Clinical Research	San Diego	California	United States	92103
10	Kaiser Permanente Medical Group San Francisco	San Francisco	California	United States	94118
11	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California	United States	90502
12	Kaiser Permanente Colorado	Denver	Colorado	United States	80205
13	National Jewish Health	Denver	Colorado	United States	80206
14	Apex Research LLC	Denver	Colorado	United States	80209
15	Dupont Circle Physician's Group	Washington	District of Columbia	United States	20009
16	Whitman-Walker Health	Washington	District of Columbia	United States	20009
17	Capital Medical Associates	Washington	District of Columbia	United States	20036
18	Medical Faculty Associates	Washington	District of Columbia	United States	20037
19	TheraFirst Medical Center	Fort Lauderdale	Florida	United States	33308
20	Gary J. Richmond,M.D.,P.A.	Fort Lauderdale	Florida	United States	33316
21	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982
22	AIDS Healthcare Foundation	Miami Beach	Florida	United States	33139
23	Tarrant County Infectious Disease Associates	Miami	Florida	United States	33133
24	Orlando Immunology Center	Orlando	Florida	United States	32803
25	AIDS Healthcare Foundation	Tampa	Florida	United States	33602
26	AIDS Research & Treatment Center of the Treasure Coast	Vero Beach	Florida	United States	32960
27	Triple O Research Institute PA	West Palm Beach	Florida	United States	33401
28	Atlanta ID Group	Atlanta	Georgia	United States	30309
29	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30312
30	Mercer University School of Medicine	Macon	Georgia	United States	31201
31	Community Research Initiative of New England	Boston	Massachusetts	United States	02111
32	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
33	Be Well Medical Center	Berkley	Michigan	United States	48072
34	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
35	The Kc Care Clinic Site 5580	Kansas City	Missouri	United States	64111
36	St. Louis University	Saint Louis	Missouri	United States	63110
37	Southampton Healthcare, Inc.	Saint Louis	Missouri	United States	63139
38	Prime Healthcare Services - St Michael's LLC d/b/a Saint Michael's Medical Center	Newark	New Jersey	United States	07102
39	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
40	Southwest CARE Center	Santa Fe	New Mexico	United States	87505
41	Jacobi Medical Center	Bronx	New York	United States	10461
42	Montefiore Medical Center	Bronx	New York	United States	10467
43	New York Hospital Queens	Flushing	New York	United States	11355
44	North Shore University Hospital	Manhasset	New York	United States	11030
45	Ricky K. Hsu, MD, PC	New York	New York	United States	10011
46	Infectious Disease Consultants, PA	Charlotte	North Carolina	United States	28209
47	Ohio State University Medical Center	Columbus	Ohio	United States	43210
48	Central Texas Clinical Research	Austin	Texas	United States	78705
49	AIDS Arms, Inc	Dallas	Texas	United States	75215
50	Southwest Infectious Disease Clinical Research, Inc	Dallas	Texas	United States	75219
51	North Texas Infectious Diseases Consulants	Dallas	Texas	United States	75246
52	AIDS Arms, Inc./Trinity Health & Wellness Center	Fort Worth	Texas	United States	76104
53	Therapeutic Concepts, PA	Houston	Texas	United States	77004
54	Gordon E. Crofoot MD PA	Houston	Texas	United States	77098
55	Peter Shalit, MD	Seattle	Washington	United States	98104
56	Premier Clinical Research	Spokane	Washington	United States	99202
57	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
58	CHU Saint-Pierre of Brussels	Brussels		Belgium	1000
59	Vancouver Infectious Disease Research and Care Centre	Vancouver	British Columbia	Canada	V6Z 2C7
60	Ottawa Hospital-General Campus	Ottawa	Ontario	Canada	K1Y 4E9
61	Maple Leaf Medical Clinic/Maple Leaf Research	Toronto	Ontario	Canada	M5B 1L6
62	University Health Network/Toronto General Hospital	Toronto	Ontario	Canada	M5G 2N2
63	University Hospital of Montpellier (CHU-Gui de Chauliac)	Montpellier		France	34295
64	CHU de Nantes Hopital de l'Hotel Dieu	Nantes		France	44093
65	Hopital Bichat Claude Bernard	Paris		France	75018
66	Hôpital Tenon	Paris		France	75020
67	Centre Hospitalier de Tourcoing	Tourcoing		France	59208
68	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo		Italy	24127
69	IRCCS Ospedale San Raffaele, Centro San Luigi	Milano		Italy	20127
70	Hope Clinical Research	San Juan		Puerto Rico	00901
71	Clinical Research Puerto Rico Inc	San Juan		Puerto Rico	00909
72	University of Puerto Rico School of Medicine	San Juan		Puerto Rico	00935
73	Brighton and Sussex University Hospitals	Brighton		United Kingdom	BN2 1ES
74	Barts Health NHS Trust	London		United Kingdom	E1 1BB
75	Royal Free London NHS Foundation Trust	London		United Kingdom	NW3 2QG
76	King's College Hospital	London		United Kingdom	SE5 9RJ
77	Chelsea and Westminster Hospital	London		United Kingdom	SW10 9TH
78	Manchester Centre for Sexual Health	Manchester		United Kingdom	M13 0FH

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02121795
• Other Study ID Numbers: GS-US-311-1089; 2013-005138-39
• First Posted: Apr 24, 2014
• Last Update Posted: Mar 12, 2020
• Last Verified: Feb 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
• Keywords provided by Gilead Sciences: HIV; HIV-1 Positive; Virologically-suppressed
• Additional relevant MeSH terms: Anti-Retroviral Agents

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in North America and Europe. The first participant was screened on 06 May 2014. The last study visit occurred on 1 March 2019.
Pre-assignment Detail	780 participants were screened.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: emtricitabine/tenofovir alafenamide (F/TAF) (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks. Open-Label Phase: After Week 96, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks. Open-Label Phase: After Week 96, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program.
Period Title: Double-Blind Phase
STARTED	334	334
Safety Analysis Set	333	330
COMPLETED	296	300
NOT COMPLETED	38	34
Period Title: Double-Blind Phase
STARTED	33	31
COMPLETED	21	21
NOT COMPLETED	12	10

Baseline Characteristics

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent	Total
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.	Total of all reporting groups
Overall Participants	333	330	663
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47 (9.9)	48 (9.7)	48 (9.8)
Sex: Female, Male (Count of Participants)
Female	48 14.4%	54 16.4%	102 15.4%
Male	285 85.6%	276 83.6%	561 84.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	48 14.4%	78 23.6%	126 19%
Not Hispanic or Latino	285 85.6%	252 76.4%	537 81%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	2 0.6%	1 0.3%	3 0.5%
Asian	6 1.8%	0 0%	6 0.9%
Black	69 20.7%	67 20.3%	136 20.5%
Native Hawaiian or Pacific Islander	2 0.6%	1 0.3%	3 0.5%
White	244 73.3%	253 76.7%	497 75%
Not Permitted	1 0.3%	1 0.3%	2 0.3%
Other	9 2.7%	7 2.1%	16 2.4%
Region of Enrollment (participants) [Number]
Canada	5 1.5%	9 2.7%	14 2.1%
Belgium	3 0.9%	3 0.9%	6 0.9%
United States	282 84.7%	274 83%	556 83.9%
Italy	2 0.6%	6 1.8%	8 1.2%
United Kingdom	23 6.9%	17 5.2%	40 6%
France	18 5.4%	21 6.4%	39 5.9%
Baseline Third Agent (participants) [Number]
Atazanavir boosted with ritonavir (ATV/r)	53 15.9%	50 15.2%	103 15.5%
Darunavir boosted with ritonavir (DRV/r)	84 25.2%	82 24.8%	166 25%
Lopinavir boosted with ritonavir (LPV/r)	18 5.4%	18 5.5%	36 5.4%
Dolutegravir (DTG)	26 7.8%	23 7%	49 7.4%
Efavirenz (EFV)	8 2.4%	6 1.8%	14 2.1%
Maraviroc (MVC)	1 0.3%	6 1.8%	7 1.1%
Nevirapine (NVP)	74 22.2%	66 20%	140 21.1%
Raltegravir (RAL)	66 19.8%	73 22.1%	139 21%
Rilpivirine (RPV)	3 0.9%	6 1.8%	9 1.4%
HIV-1 RNA Categories (participants) [Number]
< 50 copies/mL	329 98.8%	326 98.8%	655 98.8%
>= 50 copies/mL	4 1.2%	4 1.2%	8 1.2%
CD4 Cell Count (cells/µL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/µL]	691 (272.6)	667 (272.3)	679 (272.5)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis
Description	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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

The Full Analysis Set included all participants who were randomized into the study and received at least one dose of study drug.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	333	330
Number [percentage of participants]	94.3 28.3%	93.0 28.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	F/TAF + 3rd Agent, FTC/TDF + 3rd Agent
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was assessed using a conventional 95.002% confidence interval (CI) approach, with a noninferiority margin of 10%.
Statistical Test of Hypothesis	p-Value	0.5
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	P-value was from Cochran-Mantel-Haenszel (CMH) test stratified by third agent.
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95.002%; -2.5 to 5.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentages of virologic success between treatment groups and its 95.002% CI were calculated based on the Mantel-Haenszel (MH) proportions adjusted by the third agent stratum.

2. Secondary Outcome

Title	Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Description	Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Hip DXA Analysis Set (participants who were randomized and received at least one dose of study drug and had nonmissing baseline hip BMD data) with available data were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	304	305
Mean (Standard Deviation) [percentage change]	1.236 (2.6602)	-0.071 (2.3316)

3. Secondary Outcome

Title	Percentage Change From Baseline in Spine BMD at Week 48
Description	Spine BMD was assessed by DXA scan.
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Spine DXA Analysis Set (participants who were randomized and received at least one dose of study drug and had nonmissing baseline spine BMD data) with available data were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	304	309
Mean (Standard Deviation) [percentage change]	1.662 (3.1279)	-0.109 (3.3476)

4. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis
Description	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	333	330
Number [percentage of participants]	91.6 27.5%	90.9 27.5%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with on-treatment data were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	313	311
Mean (Standard Deviation) [cells/μL]	20 (161.8)	21 (152.7)

6. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis
Description	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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 96

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	333	330
Number [percentage of participants]	83.5 25.1%	86.1 26.1%

7. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis
Description	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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 96

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	333	330
Number [percentage of participants]	88.6 26.6%	89.1 27%

8. Secondary Outcome

Title	Percentage Change From Baseline in Hip BMD at Week 96
Description	Hip BMD was assessed by DXA scan.
Time Frame	Baseline; Week 96

Outcome Measure Data

Analysis Population Description

Participants in the Hip DXA Analysis Set with available data were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	291	292
Mean (Standard Deviation) [percentage change]	1.856 (3.2195)	-0.289 (2.9912)

9. Secondary Outcome

Title	Percentage Change From Baseline in Spine BMD at Week 96
Description	Spine BMD was assessed by DXA scan.
Time Frame	Baseline; Week 96

Outcome Measure Data

Analysis Population Description

Participants in the Spine DXA Analysis Set with available data were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	290	296
Mean (Standard Deviation) [percentage change]	2.159 (3.8374)	-0.109 (3.6738)

10. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count at Week 96
Time Frame	Baseline; Week 96

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with on-treatment data were analyzed.

Arm/Group Title	F/TAF + 3rd Agent	FTC/TDF + 3rd Agent
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Measure Participants	299	296
Mean (Standard Deviation) [cells/μL]	50 (198.7)	46 (169.4)

Adverse Events

Time Frame	First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days
Adverse Event Reporting Description	The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Arm/Group Title	F/TAF + 3rd Agent (Double-Blind)		FTC/TDF + 3rd Agent (Double-Blind)		Open-Label F/TAF From F/TAF		Open-Label F/TAF From FTC/TDF
Arm/Group Description	Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg tablet) + FTC/TDF placebo tablet + third agent administered orally once daily for at least 96 weeks.		Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.		Open-Label Phase: F/TAF (200/25 mg or 200/10 mg) tablet orally once daily until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program in participants from the F/TAF + 3rd Agent group.		Open-Label Phase: F/TAF (200/25 mg or 200/10 mg) tablet orally once daily until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program in participants from the FTC/TDF + 3rd Agent group.
All Cause Mortality
	F/TAF + 3rd Agent (Double-Blind)		FTC/TDF + 3rd Agent (Double-Blind)		Open-Label F/TAF From F/TAF		Open-Label F/TAF From FTC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/333 (0.6%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Serious Adverse Events
	F/TAF + 3rd Agent (Double-Blind)		FTC/TDF + 3rd Agent (Double-Blind)		Open-Label F/TAF From F/TAF		Open-Label F/TAF From FTC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/333 (8.7%)		31/330 (9.4%)		2/33 (6.1%)		3/31 (9.7%)
Cardiac disorders
Myocardial infarction	0/333 (0%)		0/330 (0%)		0/33 (0%)		1/31 (3.2%)
Ventricular extrasystoles	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Gastrointestinal disorders
Abdominal pain	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Abdominal pain upper	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Chronic gastritis	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Colitis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Constipation	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Diarrhoea	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Haematemesis	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Haemorrhoids	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Intestinal stenosis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Intestinal ulcer	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Obstructive pancreatitis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Oesophageal stenosis	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Pancreatitis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Pancreatitis acute	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
General disorders
Chest pain	2/333 (0.6%)		1/330 (0.3%)		1/33 (3%)		0/31 (0%)
Drowning	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Mucosal inflammation	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Hepatobiliary disorders
Cholecystitis	1/333 (0.3%)		2/330 (0.6%)		0/33 (0%)		0/31 (0%)
Cholelithiasis	1/333 (0.3%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Cholelithiasis obstructive	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Infections and infestations
Acute hepatitis C	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Arthritis bacterial	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Bone tuberculosis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Diverticulitis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Enteritis infectious	0/333 (0%)		0/330 (0%)		0/33 (0%)		1/31 (3.2%)
Escherichia urinary tract infection	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Gastrointestinal infection	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Herpes zoster	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Influenza	0/333 (0%)		0/330 (0%)		1/33 (3%)		0/31 (0%)
Laryngitis	0/333 (0%)		0/330 (0%)		1/33 (3%)		0/31 (0%)
Localised infection	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Lung infection	0/333 (0%)		0/330 (0%)		1/33 (3%)		0/31 (0%)
Mycobacterium abscessus infection	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Oesophagitis bacterial	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Pneumonia	0/333 (0%)		3/330 (0.9%)		0/33 (0%)		0/31 (0%)
Prostatitis Escherichia coli	0/333 (0%)		0/330 (0%)		1/33 (3%)		0/31 (0%)
Pyelonephritis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Subcutaneous abscess	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Anastomotic stenosis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Ankle fracture	0/333 (0%)		2/330 (0.6%)		0/33 (0%)		0/31 (0%)
Limb injury	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Overdose	1/333 (0.3%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Investigations
Lipase increased	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Metabolism and nutrition disorders
Dehydration	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Fluid overload	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/333 (0%)		0/330 (0%)		0/33 (0%)		1/31 (3.2%)
Arthritis	0/333 (0%)		0/330 (0%)		0/33 (0%)		1/31 (3.2%)
Back pain	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Intervertebral disc protrusion	3/333 (0.9%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Neck pain	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Osteoarthritis	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Rhabdomyolysis	2/333 (0.6%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Lymphoma	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Metastases to lung	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Metastases to lymph nodes	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Tonsil cancer	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Nervous system disorders
Carotid artery stenosis	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Dizziness exertional	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Encephalopathy	0/333 (0%)		2/330 (0.6%)		0/33 (0%)		0/31 (0%)
Headache	1/333 (0.3%)		2/330 (0.6%)		0/33 (0%)		0/31 (0%)
Loss of consciousness	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Syncope	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Psychiatric disorders
Alcoholism	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Delirium	0/333 (0%)		0/330 (0%)		1/33 (3%)		0/31 (0%)
Depressed mood	0/333 (0%)		0/330 (0%)		1/33 (3%)		0/31 (0%)
Depression	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Suicide attempt	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Renal and urinary disorders
Nephrolithiasis	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Renal colic	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/333 (0.3%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Dyspnoea	1/333 (0.3%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Pleural effusion	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Pneumonia aspiration	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Pneumothorax	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Pulmonary embolism	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Respiratory failure	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Vascular disorders
Aortic aneurysm	0/333 (0%)		1/330 (0.3%)		0/33 (0%)		0/31 (0%)
Venous thrombosis limb	1/333 (0.3%)		0/330 (0%)		0/33 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	F/TAF + 3rd Agent (Double-Blind)		FTC/TDF + 3rd Agent (Double-Blind)		Open-Label F/TAF From F/TAF		Open-Label F/TAF From FTC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	242/333 (72.7%)		226/330 (68.5%)		12/33 (36.4%)		13/31 (41.9%)
Gastrointestinal disorders
Diarrhoea	44/333 (13.2%)		42/330 (12.7%)		1/33 (3%)		0/31 (0%)
Nausea	23/333 (6.9%)		19/330 (5.8%)		0/33 (0%)		0/31 (0%)
General disorders
Fatigue	26/333 (7.8%)		23/330 (7%)		0/33 (0%)		0/31 (0%)
Influenza like illness	6/333 (1.8%)		10/330 (3%)		0/33 (0%)		2/31 (6.5%)
Pyrexia	6/333 (1.8%)		17/330 (5.2%)		0/33 (0%)		0/31 (0%)
Infections and infestations
Bronchitis	32/333 (9.6%)		26/330 (7.9%)		1/33 (3%)		1/31 (3.2%)
Fungal skin infection	1/333 (0.3%)		2/330 (0.6%)		0/33 (0%)		2/31 (6.5%)
Gastroenteritis	11/333 (3.3%)		8/330 (2.4%)		2/33 (6.1%)		0/31 (0%)
Influenza	23/333 (6.9%)		15/330 (4.5%)		0/33 (0%)		2/31 (6.5%)
Nasopharyngitis	43/333 (12.9%)		27/330 (8.2%)		4/33 (12.1%)		2/31 (6.5%)
Onychomycosis	6/333 (1.8%)		3/330 (0.9%)		0/33 (0%)		3/31 (9.7%)
Sinusitis	23/333 (6.9%)		28/330 (8.5%)		2/33 (6.1%)		3/31 (9.7%)
Syphilis	18/333 (5.4%)		7/330 (2.1%)		3/33 (9.1%)		2/31 (6.5%)
Upper respiratory tract infection	54/333 (16.2%)		67/330 (20.3%)		1/33 (3%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	35/333 (10.5%)		23/330 (7%)		0/33 (0%)		2/31 (6.5%)
Back pain	37/333 (11.1%)		28/330 (8.5%)		3/33 (9.1%)		2/31 (6.5%)
Pain in extremity	26/333 (7.8%)		22/330 (6.7%)		0/33 (0%)		0/31 (0%)
Nervous system disorders
Headache	33/333 (9.9%)		22/330 (6.7%)		0/33 (0%)		1/31 (3.2%)
Psychiatric disorders
Anxiety	15/333 (4.5%)		20/330 (6.1%)		2/33 (6.1%)		1/31 (3.2%)
Insomnia	15/333 (4.5%)		13/330 (3.9%)		0/33 (0%)		2/31 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	37/333 (11.1%)		20/330 (6.1%)		2/33 (6.1%)		2/31 (6.5%)
Skin and subcutaneous tissue disorders
Rash	19/333 (5.7%)		11/330 (3.3%)		1/33 (3%)		0/31 (0%)
Vascular disorders
Hypertension	16/333 (4.8%)		20/330 (6.1%)		0/33 (0%)		0/31 (0%)

Limitations/Caveats

There were no limitations affecting the analysis or results.

More Information

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