Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01968551
• Collaborator: (none)
• Enrollment: 158
• Locations: 62
• Arms: 3
• Actual Duration (Months): 34.2
• Patients Per Site: 2.5
• 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 elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose combination (FDC) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in virologically suppressed, HIV-1 positive participants with HIV-1 RNA <50 copies/mL at Week 24.

This study consists of 48 weeks of open-label phase followed by an optional Extension Phase in which all the participants will receive E/C/F/TAF+DRV.

Condition or Disease	Intervention/Treatment	Phase
HIV-1; HIV Infections; Acquired Immunodeficiency Syndrome	Drug: E/C/F/TAF; Drug: DRV; Drug: Baseline DRV- containing ARV regimen	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
• Actual Study Start Date: Sep 3, 2013
• Actual Primary Completion Date: Jul 21, 2015
• Actual Study Completion Date: Jul 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya® ; Drug: DRV; 800 mg tablet administered orally once daily
Experimental: Cohort 2, Treatment Group 1 Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya® ; Drug: DRV; 800 mg tablet administered orally once daily
Active Comparator: Cohort 2, Treatment Group 2 Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.	Drug: Baseline DRV- containing ARV regimen; Participants will take their baseline DRV- containing ARV regimen as prescribed.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24 [Week 24]

   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient'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 in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48 [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 patient'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 24 [Baseline; Week 24]

3. Change From Baseline in CD4+ Cell Count at Week 48 [Baseline; 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:

• Ability to understand and sign a written informed consent form

• History of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents

• Plasma HIV-1 RNA levels < 50 copies/mL at screening. Virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma HIV-1 RNA levels (< 50 copies/mL) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation.

• Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily), or have never received integrase inhibitor, or have documentation of genotype/phenotype within 12 months prior to current regimen which must show no evidence of resistance to integrase inhibitors

• Normal ECG

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

• Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)

• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

• Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^{3; platelets ≥ 50,000/mm}3; hemoglobin ≥ 8.5 g/dL)

• Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)

• A female individual is eligible to enter the study if it is confirmed that she is:

• Not pregnant or nursing

• Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation (for ≥ 12 months) of previously occurring menses), or

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

• Female individuals 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.

• Male individuals 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.

• Male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4 cell count and/or percentage criteria)

• Hepatitis B surface antigen (HBsAg) positive

• Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study.

• Must not have Q151M, T69ins, or > 3 thymidine analogue mutations (TAMS) present on documented historic genotype report

• Individuals experiencing decompensated cirrhosis

• Females who are breastfeeding

• Positive serum pregnancy test

• Have an implanted defibrillator or pacemaker

• Current alcohol or substance use that may interfere with individual's study compliance

• A history of malignancy within the past 5 years 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

• Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements

• Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial

• Individuals receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or DRV; or individuals with any known allergies to the study drugs.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pueblo Family Physicians, Ltd.	Phoenix	Arizona	United States	85015
2	Pacific Oaks Medical Group	Beverly Hills	California	United States	90211
3	Kaiser Permanente	Hayward	California	United States	94545
4	Long Beach Education and Research Consultants	Long Beach	California	United States	90813
5	Peter J Ruane, MD, Inc.	Los Angeles	California	United States	90036
6	Kaiser Permanente Medical Group	Sacramento	California	United States	95825
7	Kaiser San Francisco Division of Research	San Francisco	California	United States	94118
8	Dupont Circle Physician's Group	Washington	District of Columbia	United States	20009
9	Midland Florida Clinical Research Center, LLC	DeLand	Florida	United States	32720
10	Therafirst Medical Center	Fort Lauderdale	Florida	United States	33308
11	Gary J.Richmond, MD, P.A.	Fort Lauderdale	Florida	United States	33316
12	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982
13	Orlando Immunology Center	Orlando	Florida	United States	32803
14	Valuhealthmd/Idocf	Orlando	Florida	United States	32806
15	Infectious Diseases Associates of NW FL	Pensacola	Florida	United States	32504
16	Hillsborough County Health Department	Tampa	Florida	United States	33602
17	St. Joseph's Comprehensive Research Institute	Tampa	Florida	United States	33614
18	AIDS Research and Treatment Center of the Treasure Coast	Vero Beach	Florida	United States	32960
19	Triple O Research Institute PA	West Palm Beach	Florida	United States	33401
20	Atlanta ID Group	Atlanta	Georgia	United States	30309
21	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30312
22	Mercer University, Mercer Medicine	Macon	Georgia	United States	31201
23	The Ruth M. Rothstein CORE Center	Chicago	Illinois	United States	60612
24	Howard Brown Health Center	Chicago	Illinois	United States	60613
25	Johns Hopkins University	Lutherville	Maryland	United States	21093
26	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
27	Harvard Medical School	Boston	Massachusetts	United States	02215
28	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts	United States	01199
29	Henry Ford Health System	Detroit	Michigan	United States	48202
30	Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55404
31	The Kansas City Free Health Clinic/ KC Care Clinic	Kansas City	Missouri	United States	64111
32	Central West Clinical Research	Saint Louis	Missouri	United States	63108
33	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
34	Southwest CARE Center	Santa Fe	New Mexico	United States	87505
35	Albany Medical College	Albany	New York	United States	12208
36	New York Hospital Queens	Flushing	New York	United States	11355
37	Beth Israel Medical Center	New York	New York	United States	10003
38	Weill Medical College	New York	New York	United States	10011
39	University of Rochester	Rochester	New York	United States	14642
40	Carolinas Medical Center--Myer's Park	Charlotte	North Carolina	United States	28207
41	Duke University Health System	Durham	North Carolina	United States	27710
42	East Carolina University The Brody School of Medicine, Infectious Diseases	Greenville	North Carolina	United States	27858
43	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
44	Summa Health System CARE Center	Akron	Ohio	United States	44304
45	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
46	University Of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
47	Philadelphia FIGHT	Philadelphia	Pennsylvania	United States	19107
48	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
49	The Miriam Hospital	Providence	Rhode Island	United States	02906
50	North Texas infectious Diseases Consultants, PA	Dallas	Texas	United States	75246
51	Therapeutic Concepts, PA	Houston	Texas	United States	77004
52	Gordon E. Crofoot MD PA	Houston	Texas	United States	77098
53	DCOL Center for Clinical Research	Longview	Texas	United States	75606
54	University of Utah	Salt Lake City	Utah	United States	84102
55	Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)	Annandale	Virginia	United States	220003
56	Peter Shalit, MD	Seattle	Washington	United States	98104
57	Southern Alberta Clinic	Calgary	Alberta	Canada	T2R 0X7
58	Vancouver ID Research & Care Centre Society	Vancouver	British Columbia	Canada	V6Z2C7
59	Wrha - Health Sciences Centre Winnipeg	Winnipeg	Manitoba	Canada	R3A 1R9
60	Ottawa Hospital - General Campus	Ottawa	Ontario	Canada	K1H 8L6
61	Maple Leaf Research	Toronto	Ontario	Canada	M5G1K2
62	Clinique médicale L'actuel	Montreal	Quebec	Canada	H2l 4P9

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• Greg Huhn, Pablo Tebas, Joel Gallant et al. Strategic Simplification: the Efficacy and Safety of Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Plus Darunavir (DRV) in Treatment-Experienced HIV-1-Infected Adults (NCT01968551). IDWeek; 2015 San Diego, CA Oct. 7-11.
• Huhn GD, Tebas P, Gallant J, Wilkin T, Cheng A, Yan M, Zhong L, Callebaut C, Custodio JM, Fordyce MW, Das M, McCallister S. A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):193-200. doi: 10.1097/QAI.0000000000001193.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01968551
• Other Study ID Numbers: GS-US-292-0119
• First Posted: Oct 24, 2013
• Last Update Posted: Nov 16, 2018
• Last Verified: Jul 1, 2017

• 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-1; HIV; Treatment-Experienced
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States and Canada. The first participant was screened on 3 September 2013. The last study visit occurred on 09 July 2016.
Pre-assignment Detail	231 participants were screened.

Arm/Group Title	Cohort 1: E/C/F/TAF+DRV	Cohort 2: E/C/F/TAF+DRV	Cohort 2: Stay on Baseline Regimen (SBR)
Arm/Group Description	Open-Label (OL) Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet plus Darunavir (DRV) (800 mg) tablet administered orally once daily for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus Darunavir (DRV) (800 mg) tablet administered orally once daily	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks. Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily
Period Title: Open Label Phase (48 Weeks)
STARTED	22	90	46
COMPLETED	20	87	41
NOT COMPLETED	2	3	5
Period Title: Open Label Phase (48 Weeks)
STARTED	20	87	34
COMPLETED	19	86	30
NOT COMPLETED	1	1	4

Baseline Characteristics

Arm/Group Title	Cohort 1: E/C/F/TAF+DRV	Cohort 2: E/C/F/TAF+DRV	Cohort 2: SBR	Total
Arm/Group Description	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily with food for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily with food for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Total of all reporting groups
Overall Participants	21	89	46	156
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53 (5.7)	49 (8.2)	47 (9.4)	49 (8.4)
Sex: Female, Male (Count of Participants)
Female	8 38.1%	16 18%	18 39.1%	42 26.9%
Male	13 61.9%	73 82%	28 60.9%	114 73.1%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%	1 1.1%	0 0%	1 0.6%
Asian	0 0%	1 1.1%	0 0%	1 0.6%
Black	12 57.1%	35 39.3%	26 56.5%	73 46.8%
Native Hawaiian or Pacific Islander	0 0%	1 1.1%	0 0%	1 0.6%
White	9 42.9%	51 57.3%	17 37%	77 49.4%
Not Permitted	0 0%	0 0%	0 0%	0 0%
Other	0 0%	0 0%	3 6.5%	3 1.9%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	2 9.5%	12 13.5%	7 15.2%	21 13.5%
Not Hispanic or Latino	19 90.5%	77 86.5%	39 84.8%	135 86.5%
Not Permitted	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	0 0%	9 10.1%	3 6.5%	12 7.7%
United States	21 100%	80 89.9%	43 93.5%	144 92.3%
HIV-1 RNA Category (participants) [Number]
< 50 copies/mL	19 90.5%	87 97.8%	46 100%	152 97.4%
≥ 50 copies/mL	2 9.5%	2 2.2%	0 0%	4 2.6%
CD4 Cell Count (cells/µL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/µL]	700 (372.5)	562 (260.8)	571 (245.2)	583 (275.9)
CD4 Cell Count Category (participants) [Number]
< 200 cells/µL	1 4.8%	5 5.6%	1 2.2%	7 4.5%
≥ 200 to < 350 cells/µL	3 14.3%	15 16.9%	7 15.2%	25 16%
≥ 350 cells/µL	17 81%	69 77.5%	38 82.6%	124 79.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
Description	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient'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 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in Cohort 2, included all participants who (1) were randomized to Cohort 2 and (2) received at least 1 dose of study drug during the open-label Phase.

Arm/Group Title	Cohort 2: E/C/F/TAF+DRV	Cohort 2: Stay on Baseline Regimen (SBR)
Arm/Group Description	Open-Label Phase: E/C/F/TDF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks. Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily
Measure Participants	89	46
Number [percentage of participants]	96.6 460%	91.3 102.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: E/C/F/TAF+DRV, Cohort 2: Stay on Baseline Regimen (SBR)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Null Hypothesis: In Cohort 2, the group switching to E/C/F/TAF + DRV was at least 12% lower than the group remaining on SBR with respect to percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24. Alternative Hypothesis: In Cohort 2, the group switching to E/C/F/TAF + DRV is less than 12% lower than the group remaining on SBR with respect to the proportion of participants with HIV-1 RNA<50 copies/mL at Week 24.
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95.001%; -3.4 to 17.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentages of virologic success and its 95.001% confidence interval (CI) calculation was based on exact method. The exact CI was estimated based on unconditional exact method using 2 inverted 1-sided tests with standardized statistic.

2. Secondary Outcome

Title	Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48
Description	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient'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 included participants who (1) were randomized into Cohort 2 and (2) had received at least one dose of study drug during the OL phase of the study.

Arm/Group Title	Cohort 2: E/C/F/TAF+DRV	Cohort 2: Stay on Baseline Regimen (SBR)
Arm/Group Description	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily
Measure Participants	89	46
Number [percentage of participants]	94.4 449.5%	76.1 85.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: E/C/F/TAF+DRV, Cohort 2: Stay on Baseline Regimen (SBR)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Null Hypothesis: In Cohort 2, the group switching to E/C/F/TAF + DRV was at least 12% lower than the group remaining on SBR with respect to percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48. Alternative Hypothesis: In Cohort 2, the group switching to E/C/F/TAF + DRV is less than 12% lower than the group remaining on SBR with respect to the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48.
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	18.3
	Confidence Interval	(2-Sided) 95.001%; 3.5 to 33.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentages of virologic success and its 95.001% CI were calculated based on exact method. The exact CI was estimated based on unconditional exact method using 2 inverted 1-sided tests with the standardized statistic.

3. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count at Week 24
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included participants who (1) were randomized into Cohort 2 and (2) had received at least one dose of study drug during the OL phase of the study. Participants with available data were analyzed.

Arm/Group Title	Cohort 2: E/C/F/TAF+DRV	Cohort 2: Stay on Baseline Regimen (SBR)
Arm/Group Description	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks. Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily
Measure Participants	88	42
Mean (Standard Deviation) [cells/μL]	23 (155.2)	12 (100.9)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included participants who (1) were randomized into Cohort 2 and (2) had received at least one dose of study drug during the OL phase of the study. Participants with available data were analyzed.

Arm/Group Title	Cohort 2: E/C/F/TAF+DRV	Cohort 2: Stay on Baseline Regimen (SBR)
Arm/Group Description	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800mg) tablet administered orally once daily for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily	Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks. Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily
Measure Participants	85	39
Mean (Standard Deviation) [cells/μL]	5 (162.6)	41 (104.2)

Adverse Events

Time Frame	Up to a maximum of 97.4 weeks (duration of exposure: Cohort 1 and Cohort 2 = 48 weeks; All E/C/F/TAF = up to maximum of 97.4 weeks)
Adverse Event Reporting Description	Safety Analysis Set included all participants in: Cohort 1: who were enrolled into Cohort 1 and received at least 1 dose of study drug during the open-label Phase Cohort 2: who were randomized into Cohort 2 and received at least 1 dose of study drug during the open-label Phase All E/C/F/TAF: who received at least 1 dose of E/C/F/TAF during the Open-Label Phase or Extension Phase For Cohort 1 and Cohort 2, only the adverse events that occurred during the Open-Label Phase are reported.
Arm/Group Title	Cohort 1: E/C/F/TAF+DRV		Cohort 2: E/C/F/TAF+DRV		Cohort 2: SBR		All E/C/F/TAF
Arm/Group Description	Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily with food for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily		Open-Label Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily with food for up to 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily		Open-Label Phase: Participants stayed on their baseline DRV- containing regimen administered according to the prescribing information for up to 48 weeks. Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus DRV (800 mg) tablet administered orally once daily		Open- label or Extension Phase: All participants received E/C/F/TAF.
All Cause Mortality
	Cohort 1: E/C/F/TAF+DRV		Cohort 2: E/C/F/TAF+DRV		Cohort 2: SBR		All E/C/F/TAF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1: E/C/F/TAF+DRV		Cohort 2: E/C/F/TAF+DRV		Cohort 2: SBR		All E/C/F/TAF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		9/89 (10.1%)		1/46 (2.2%)		20/144 (13.9%)
Cardiac disorders
Angina pectoris	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Angina unstable	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Coronary artery disease	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Myocardial infarction	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Tachycardia	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Gastrointestinal disorders
Haemorrhoidal haemorrhage	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Pancreatitis	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Retroperitoneal haemorrhage	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Small intestinal obstruction	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		2/144 (1.4%)
General disorders
Chest pain	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		2/144 (1.4%)
Death	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Non-cardiac chest pain	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Infections and infestations
Bronchitis	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Cellulitis	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Clostridium difficile colitis	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Gastroenteritis	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Gastroenteritis clostridial	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Pneumonia bacterial	1/21 (4.8%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Sepsis	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Urinary tract infection	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Injury, poisoning and procedural complications
Rib fracture	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Splenic rupture	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Subdural haematoma	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Vascular pseudoaneurysm	0/21 (0%)		0/89 (0%)		1/46 (2.2%)		0/144 (0%)
Metabolism and nutrition disorders
Obesity	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Prostate cancer	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Nervous system disorders
Syncope	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Psychiatric disorders
Alcohol abuse	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Alcohol withdrawal syndrome	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Delirium	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Substance abuse	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/21 (0%)		1/89 (1.1%)		0/46 (0%)		1/144 (0.7%)
Pneumothorax	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Vascular disorders
Hypotension	0/21 (0%)		0/89 (0%)		0/46 (0%)		1/144 (0.7%)
Other (Not Including Serious) Adverse Events
	Cohort 1: E/C/F/TAF+DRV		Cohort 2: E/C/F/TAF+DRV		Cohort 2: SBR		All E/C/F/TAF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/21 (61.9%)		56/89 (62.9%)		28/46 (60.9%)		104/144 (72.2%)
Gastrointestinal disorders
Abdominal pain	0/21 (0%)		5/89 (5.6%)		2/46 (4.3%)		6/144 (4.2%)
Constipation	0/21 (0%)		5/89 (5.6%)		0/46 (0%)		7/144 (4.9%)
Diarrhoea	0/21 (0%)		4/89 (4.5%)		4/46 (8.7%)		10/144 (6.9%)
Gastrooesophageal reflux disease	2/21 (9.5%)		2/89 (2.2%)		1/46 (2.2%)		7/144 (4.9%)
Nausea	0/21 (0%)		5/89 (5.6%)		0/46 (0%)		8/144 (5.6%)
Vomiting	0/21 (0%)		3/89 (3.4%)		2/46 (4.3%)		10/144 (6.9%)
General disorders
Fatigue	0/21 (0%)		4/89 (4.5%)		2/46 (4.3%)		8/144 (5.6%)
Infections and infestations
Acute sinusitis	4/21 (19%)		1/89 (1.1%)		0/46 (0%)		9/144 (6.3%)
Bronchitis	3/21 (14.3%)		6/89 (6.7%)		1/46 (2.2%)		14/144 (9.7%)
Influenza	0/21 (0%)		1/89 (1.1%)		3/46 (6.5%)		3/144 (2.1%)
Nasopharyngitis	0/21 (0%)		6/89 (6.7%)		2/46 (4.3%)		8/144 (5.6%)
Oral candidiasis	2/21 (9.5%)		1/89 (1.1%)		0/46 (0%)		3/144 (2.1%)
Otitis media	2/21 (9.5%)		3/89 (3.4%)		0/46 (0%)		7/144 (4.9%)
Pharyngitis	0/21 (0%)		5/89 (5.6%)		1/46 (2.2%)		7/144 (4.9%)
Sinusitis	3/21 (14.3%)		6/89 (6.7%)		4/46 (8.7%)		15/144 (10.4%)
Upper respiratory tract infection	3/21 (14.3%)		10/89 (11.2%)		2/46 (4.3%)		27/144 (18.8%)
Viral upper respiratory tract infection	1/21 (4.8%)		4/89 (4.5%)		2/46 (4.3%)		8/144 (5.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/21 (9.5%)		3/89 (3.4%)		2/46 (4.3%)		7/144 (4.9%)
Back pain	0/21 (0%)		11/89 (12.4%)		3/46 (6.5%)		12/144 (8.3%)
Musculoskeletal pain	1/21 (4.8%)		2/89 (2.2%)		3/46 (6.5%)		6/144 (4.2%)
Myalgia	1/21 (4.8%)		5/89 (5.6%)		1/46 (2.2%)		8/144 (5.6%)
Pain in extremity	0/21 (0%)		4/89 (4.5%)		4/46 (8.7%)		7/144 (4.9%)
Nervous system disorders
Headache	1/21 (4.8%)		6/89 (6.7%)		0/46 (0%)		16/144 (11.1%)
Hypoaesthesia	2/21 (9.5%)		1/89 (1.1%)		0/46 (0%)		4/144 (2.8%)
Psychiatric disorders
Depression	2/21 (9.5%)		2/89 (2.2%)		0/46 (0%)		8/144 (5.6%)
Insomnia	0/21 (0%)		4/89 (4.5%)		1/46 (2.2%)		9/144 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/21 (4.8%)		4/89 (4.5%)		3/46 (6.5%)		10/144 (6.9%)
Vascular disorders
Hypertension	0/21 (0%)		4/89 (4.5%)		0/46 (0%)		8/144 (5.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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