Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01106586
• Collaborator: (none)
• Enrollment: 708
• Locations: 146
• Arms: 2
• Duration (Months): 53
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI [GS-9350])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir-boosted atazanavir (ATV/r) plus the standard of care nucleoside reverse transcriptase inhibitor (NRTI) backbone FTC/TDF (Truvada®). ATV/r + FTC/TDF was selected as the active comparator for this study as it is a preferred protease inhibitor-based regimen in guidelines for the treatment of HIV-1 infected, antiretroviral treatment-naive adults.

Condition or Disease	Intervention/Treatment	Phase
HIV; HIV Infections	Drug: Stribild; Drug: ATV; Drug: Ritonavir; Drug: FTC/TDF; Drug: Stribild Placebo; Drug: ATV Placebo; Drug: RTV Placebo; Drug: FTC/TDF Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 708 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 Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stribild	Drug: Stribild; Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR administered orally once daily; Drug: ATV Placebo; Placebo to match ATV administered orally once daily; Drug: RTV Placebo; Placebo to match RTV administered orally once daily; Drug: FTC/TDF Placebo; Placebo to match FTC/TDF administered orally once daily
Active Comparator: ATV/r + FTC/TDF	Drug: ATV; Atazanavir 300 mg capsule administered orally once daily; Drug: Ritonavir; Ritonavir (RTV; /r) 100 mg tablet administered orally once daily; Other Names: Norvir® ; Drug: FTC/TDF; FTC/TDF 200/300 mg tablet administered orally once daily; Other Names: Truvada ; Drug: Stribild Placebo; Placebo to match Stribild administered orally once daily

Outcome Measures

Primary Outcome Measures

1. The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 [Week 48]

Secondary Outcome Measures

1. The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 [Week 96]

2. The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 [Week 144]

3. The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 [Week 192]

4. The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm [Week 48]

5. The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 [Baseline; Weeks 48, 96, 144, and 192]

   Change = value of the relevant time point minus the baseline value

6. The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [Week 48]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

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

• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at screening

• No prior use of any approved or investigational antiretroviral drug for any length of time

• Screening genotype report must show sensitivity to FTC, TDF, and ATV

• Normal electrocardiogram (ECG)

• Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula)

• Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x the upper limit of the normal range (ULN)

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

• Adequate hematologic function

• Serum amylase ≤ 5 x ULN

• Males and Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug

• Age ≥ 18 years

• Life expectancy ≥ 1 year

Exclusion Criteria:

• A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening

• Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C

• Subjects experiencing decompensated cirrhosis

• Females who are breastfeeding

• Positive serum pregnancy test (female of childbearing potential)

• Implanted defibrillator or pacemaker

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

• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma

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

• Medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, or ritonavir or subjects with any known allergies to the excipients of Stribild tablets, Truvada tablets, ATV capsules or ritonavir tablets

• Participation in any other clinical trial without prior approval

• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spectrum Medical Group	Phoenix	Arizona	United States	85012
2	Health for Life Clinic PLLC	Little Rock	Arkansas	United States	72207
3	AHF Research Center	Beverly Hills	California	United States	90211
4	CSI Clinical Trials, Inc.	Costa Mesa	California	United States	92626
5	Apex Research, LLC	Denver	California	United States	80209
6	Kaiser Permanente Hospital	Hayward	California	United States	94545
7	Living Hope Clinical Foundation	Long Beach	California	United States	90813
8	Kaiser Permanente	Los Angeles	California	United States	90027
9	Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic	Los Angeles	California	United States	90028
10	Peter J Ruane, MD, Inc	Los Angeles	California	United States	90036
11	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
12	Anthony Mills MD Inc	Los Angeles	California	United States	90069
13	Orange Coast Medical Group	Newport Beach	California	United States	92663
14	Alameda County Medical Center	Oakland	California	United States	94602
15	East Bay AIDS Center	Oakland	California	United States	94609
16	Stanford University	Palo Alto	California	United States	94303
17	University of California, Davis Medical Center	Sacramento	California	United States	95817
18	Kaiser Permanente Medical Group	Sacramento	California	United States	95825
19	La Playa Medical Group and Clinical Research	San Diego	California	United States	92103
20	Metropolitan Medical	San Francisco	California	United States	94115
21	Kaiser Permanente Medical Center, Clinical Trials Unit	San Francisco	California	United States	94118
22	National Jewish Health	Denver	Colorado	United States	80206
23	Yale University HIV Clinical Trials Program	New Haven	Connecticut	United States	06033
24	The Stamford Hospital	Stamford	Connecticut	United States	06902
25	Dupont Circle Physicians Group	Washington	District of Columbia	United States	20009
26	Whitman Walker Clinic	Washington	District of Columbia	United States	20009
27	Capital Medical Associates, PC	Washington	District of Columbia	United States	20036
28	George Washington University Medical Faculty Associates	Washington	District of Columbia	United States	20037
29	Therafirst Medical Center	Fort Lauderdale	Florida	United States	33308
30	Broward Health/Comprehensive Care Center	Fort Lauderdale	Florida	United States	33311
31	Gary J. Richmond,M.D., P.A.	Fort Lauderdale	Florida	United States	33316
32	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982
33	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida	United States	33139
34	The Kinder Medical Group	Miami	Florida	United States	33133
35	Orlando Immunology Center	Orlando	Florida	United States	32803
36	IDOCF/ ValueHealthMD, LLC	Orlando	Florida	United States	32806
37	University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department	Tampa	Florida	United States	33602
38	Infectious Disease Research Institute Inc.	Tampa	Florida	United States	33614
39	St. Joseph's Comprehensive Research Institute	Tampa	Florida	United States	33615
40	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida	United States	32960
41	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
42	Infectious Disease Solutions, PC	Atlanta	Georgia	United States	30309
43	Mercer University School of Medicine	Macon	Georgia	United States	31210
44	Leahi Hospital	Honolulu	Hawaii	United States	96816
45	Ruth M. Rothstein CORE Center	Chicago	Illinois	United States	60612
46	Howard Brown Health Center	Chicago	Illinois	United States	60613
47	The Research Institute	Springfield	Massachusetts	United States	01107
48	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts	United States	01199
49	Be Well Medical Center	Berkley	Michigan	United States	48072
50	Henry Ford Health System	Detroit	Michigan	United States	48202
51	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
52	CentralWest Clinical Research	St. Louis	Missouri	United States	63108
53	Division of Infectious Diseases, St. Louis University Medical Center	St. Louis	Missouri	United States	63110
54	Southampton Healthcare	St. Louis	Missouri	United States	63139
55	ID Care	Hillsborough	New Jersey	United States	08844
56	Saint Michaels Medical Center	Newark	New Jersey	United States	07102
57	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
58	Garden State Infectious Diseases Associates, PA	Voorhees	New Jersey	United States	08043
59	Upstate ID Association	Albany	New York	United States	12208
60	Albany Medical College	Albany	New York	United States	12209
61	Montiefiore Medical Center- AIDS Center	Bronx	New York	United States	10467
62	STAR Health Care Center (SUNY Downstate)	Brooklyn	New York	United States	11203
63	North Shore University Hospital	Manhasset	New York	United States	11030
64	Greiger Clinic	Mount Vernon	New York	United States	10550
65	Beth Israel Medical Center	New York	New York	United States	10003
66	Chelsea Village Medical, PC	New York	New York	United States	10011
67	AIDS Care	Rochester	New York	United States	14604
68	Carolinas Medical Center-Myers Park	Charlotte	North Carolina	United States	28207
69	Duke University Medical Center	Durham	North Carolina	United States	27710
70	East Carolina University	Greenville	North Carolina	United States	27834
71	Rosedale Infectious Diseases	Huntersville	North Carolina	United States	28078
72	Wake Forest University Health Sciences	Winston Salem	North Carolina	United States	27157
73	Summa Health System	Akron	Ohio	United States	44304
74	Division of Infectious Diseases, Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
75	Philadelphia FIGHT	Philadelphia	Pennsylvania	United States	19107
76	University of South Carolina	Columbia	South Carolina	United States	29203
77	Nicholaos C. Bellos, MD, PA (Southwest Infectious Disease Clinical Research, Inc.)	Dallas	Texas	United States	75204
78	Trinity Health and Wellness Center/AIDS Arms, Inc.	Dallas	Texas	United States	75208
79	Tarrant County Infectious Disease Associates	Fort Worth	Texas	United States	76104
80	Garcia's Family Health Group	Harlingen	Texas	United States	78550
81	Dr. Joseph C. Gathe MD (Therapeutic Concepts, PA)	Houston	Texas	United States	77004
82	Gordon E. Crofoot MD PA	Houston	Texas	United States	77098
83	Research Access Network	Houston	Texas	United States	77098
84	DCOL Center for Clinical Research	Longview	Texas	United States	75605
85	Clinical Alliance for Research & Education, Infectious Diseases (CARE-ID)	Annandale	Virginia	United States	22003
86	Peter Shalit, M.D.	Seattle	Washington	United States	98104
87	Holdsworth House Medical practice	Darlinghurst	New South Wales	Australia	2010
88	National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales	Darlinghurst	New South Wales	Australia	2010
89	Albion Street Centre	Sydney	New South Wales	Australia	2010
90	East Sydney Doctors	Sydney	New South Wales	Australia	2010
91	Melbourne Health - Royal Melbourne Hospital Campus (Sexual Health Clinic)	Carlton	Victoria	Australia	3053
92	Alfred Hospital	Melbourne	Victoria	Australia	3004
93	Northside Clinic	Melbourne	Victoria	Australia	3068
94	Taylor Square Private Clinica	Darlinghurst		Australia	N.S.W. 2011
95	LKH Graz West	Graz		Austria	A-8010
96	Department of Dermatology, Division of Immunology, Allergy & Inf. Diseases; Medical University Vienna	Vienna		Austria	1090
97	Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital	Vienna		Austria	1140
98	CHU Saint-Pierre University Hospital	Brussels		Belgium	1000
99	Hôpital Universitaire Erasme - ULB	Brussels		Belgium	1070
100	University of Ghent	Ghent		Belgium	9000
101	Southern Alberta Clinic	Calgary	Alberta	Canada	T2R0X7
102	Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg	Winnipeg	Manitoba	Canada	R3A 1R9
103	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
104	Canadian Immunodeficiency Research Collaborative (CIRC) Inc.	Toronto	Ontario	Canada	M5B1L6
105	University Health Network, Toronto General Hospital	Toronto	Ontario	Canada	M5G 2N2
106	Clinique medicale l'Actuel	Montreal	Quebec	Canada	H2L 4P9
107	Clinique Medicale du Quartier Latin	Montreal	Quebec	Canada	H2L 5B1
108	Epidemiklinikken 5112, Rigshospitalet	Copenhagen		Denmark	2000
109	Service des Maladies Infectieuses, CHU de Caen	Caen		France	14033
110	Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales	Lyon		France	69317
111	CHU Gui de Chauliac, Maladies Infectieuses Dpt	Montpellier		France	34295
112	CHU de Nantes Hopital de l'Hotel Dieu	Nantes		France	44093
113	Centre Hospitalier Universitaire de Nice	Nice		France	06200
114	Department of Infectious Diseases, Saint-Louis hospital	Paris		France	75010
115	Hopital Saint Antoine, Service De Maladies Infectieuses	Paris		France	75012
116	Bichat Hospital	Paris		France	75018
117	Tenon Hospital, UPMC	Paris		France	75020
118	Hopital Pitie-Salpetriere	Paris		France	75651
119	Centre Hospitalier de Tourcoing	Tourcoing		France	59208
120	University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic	Bonn		Germany	53127
121	Center for HIV and Hepatogastroenterology	Duesseldorf		Germany	40237
122	Infektio Research GmbH / Infektiologikum Frankfurt	Frankfurt am Main		Germany	60311
123	Klinikum der Goethe-Universitaet, Medizinische Klinik II, Schwerpunkt HIV, Haus 68	Frankfurt am Main		Germany	60590
124	ICH Study Center Hamburg	Hamburg		Germany	20146
125	University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit	Hamburg		Germany	20246
126	University of Cologne, Department of Internal Medicine	Köln		Germany	50937
127	MUC Research GmbH	München		Germany	80335
128	Fondazione Centro San Raffaele del Monte Tabor	Milan		Italy	20127
129	National Institute for Infectious Diseases "L. Spallanzani" IRCCS	Rome		Italy	00149
130	Dipartimento di Malattie Infettive	Torino		Italy	10149
131	Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde	Guadalajara	Jalisco	Mexico	44280
132	Onze lieve vrouw gasthuis	Amsterdam		Netherlands
133	Erasmus MC, Internal Medicine, Section of Infectious Diseases	Rotterdam		Netherlands	3000 CA
134	Serviço de Doenças Infecciosas, Hospital de São João	Porto		Portugal	4202-451
135	Clinical Research Puerto Rico	San Juan		Puerto Rico	00909
136	VA Caribbean Healthcare System	San Juan		Puerto Rico	00921
137	Venhälsan, Södersjukhuset	Stockholm		Sweden	11883
138	CHUV	Lausanne	VD	Switzerland	1011
139	Ramathibodi Hospital, Mahidol University	Bangkok		Thailand	10400
140	Siriraj Hospital	Bangkok		Thailand	10700
141	Brighton and Sussex University Hospitals NHS Trust	Brighton	East Sussex	United Kingdom	BN2 1ES
142	North Manchester General Hospital	Manchester	Lancashire	United Kingdom	M8 5RB
143	Barts and the London NHS Trust	London		United Kingdom	E1 1BB
144	Homerton University Hospital	London		United Kingdom	E9 6SR
145	Chelsea and Westminster Hospital Foundation Trust	London		United Kingdom	SW10 9NH
146	St. Mary's Hospital, London (Imperial College, London)	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Marshall Fordyce, MD, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01106586
• Other Study ID Numbers: GS-US-236-0103
• First Posted: Apr 20, 2010
• Last Update Posted: Nov 11, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Gilead Sciences: HIV 1 Infection; Treatment Naive
• Additional relevant MeSH terms: HIV Infections; Ritonavir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 146 sites in 16 countries. The first participant was screened on 06 April 2010. The last study visit occurred on 18 September 2014.
Pre-assignment Detail	1017 subjects were screened.

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild® (elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg) plus placebo to match atazanavir/ritonavir (ATV/r) + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Period Title: Overall Study
STARTED	353	355
COMPLETED	68	70
NOT COMPLETED	285	285

Baseline Characteristics

Arm/Group Title	Stribild	ATV/r + FTC/TDF	Total
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily	Total of all reporting groups
Overall Participants	353	355	708
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (10.5)	39 (9.8)	38 (10.2)
Sex: Female, Male (Count of Participants)
Female	29 8.2%	39 11%	68 9.6%
Male	324 91.8%	316 89%	640 90.4%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	2 0.6%	3 0.8%	5 0.7%
Asian	17 4.8%	17 4.8%	34 4.8%
Black or African Heritage	72 20.4%	47 13.2%	119 16.8%
Native Hawaiian or Pacific Islander	1 0.3%	2 0.6%	3 0.4%
White	250 70.8%	277 78%	527 74.4%
Other	11 3.1%	9 2.5%	20 2.8%
Region of Enrollment (participants) [Number]
Portugal	1 0.3%	2 0.6%	3 0.4%
United States	197 55.8%	185 52.1%	382 54%
Thailand	7 2%	4 1.1%	11 1.6%
Austria	12 3.4%	8 2.3%	20 2.8%
United Kingdom	11 3.1%	15 4.2%	26 3.7%
Switzerland	0 0%	2 0.6%	2 0.3%
Italy	9 2.5%	5 1.4%	14 2%
France	23 6.5%	23 6.5%	46 6.5%
Mexico	3 0.8%	2 0.6%	5 0.7%
Canada	19 5.4%	22 6.2%	41 5.8%
Belgium	9 2.5%	12 3.4%	21 3%
Australia	30 8.5%	32 9%	62 8.8%
Denmark	1 0.3%	2 0.6%	3 0.4%
Netherlands	2 0.6%	4 1.1%	6 0.8%
Germany	29 8.2%	36 10.1%	65 9.2%
Sweden	0 0%	1 0.3%	1 0.1%
HIV Disease Status (participants) [Number]
Asymptomatic	285 80.7%	293 82.5%	578 81.6%
Symptomatic HIV Infections	36 10.2%	38 10.7%	74 10.5%
AIDS	32 9.1%	24 6.8%	56 7.9%
Hepatitis B Virus (HBV) Infection Status (participants) [Number]
Negative	347 98.3%	346 97.5%	693 97.9%
Positive	5 1.4%	7 2%	12 1.7%
Indeterminate	0 0%	1 0.3%	1 0.1%
Not done	1 0.3%	1 0.3%	2 0.3%
Hepatitis C Virus (HCV) Infection Status (participants) [Number]
Negative	335 94.9%	344 96.9%	679 95.9%
Positive	18 5.1%	10 2.8%	28 4%
Indeterminate	0 0%	0 0%	0 0%
Not done	0 0%	1 0.3%	1 0.1%
HIV-1 RNA Category (copies/mL) (participants) [Number]
≤ 100,000 copies/mL	203 57.5%	214 60.3%	417 58.9%
> 100,000 copies/mL	150 42.5%	141 39.7%	291 41.1%
CD4 Cell Count (/µL) (participants) [Number]
≤ 50 μL	12 3.4%	5 1.4%	17 2.4%
51 to ≤ 200 μL	42 11.9%	34 9.6%	76 10.7%
201 to ≤ 350 μL	122 34.6%	124 34.9%	246 34.7%
351 to ≤ 500 μL	122 34.6%	122 34.4%	244 34.5%
> 500 μL	55 15.6%	70 19.7%	125 17.7%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT analysis set: participants who were randomized into the study and received at least 1 dose of study drug

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	353	355
Number [percentage of participants]	89.5 25.4%	86.8 24.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stribild, ATV/r + FTC/TDF
	Comments	The null hypothesis was that the Stribild group is at least 12% worse than the ATV/r + Truvada group with respect to percentage of participants achieving HIV-1 RNA < 50 copies/mL (response rate as defined by the snapshot analysis algorithm) at Week 48; the alternative hypothesis was that the response rate in the Stribild group is less than 12% worse than that in the ATV/r + Truvada Group.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A total of 700 HIV-1 infected participants, randomized in a 1:1 ratio to 2 groups would achieve at least 95% power to establish noninferiority in Week 48 response (HIV-1 RNA < 50 copies/mL per the FDA-defined snapshot analysis) rate difference between the 2 groups. For sample size and power computation, it was assumed that both treatment groups have a response rate of 0.795, a noninferiority margin of 0.12, and that the significance level of the test is at a one-sided, 0.025 level.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95.2%; -1.9 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	To preserve the overall alpha level: 0.05, accounting for 2 interim analyses for Independent Data Monitoring Committee meetings, the 95.2% CI was computed using normal approximation stratified by baseline HIV-1 RNA (≤ 100,000 or > 100,000 copies/mL).

2. Secondary Outcome

Title	The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	353	355
Number [percentage of participants]	83.3 23.6%	82.3 23.2%

3. Secondary Outcome

Title	The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144
Time Frame	Week 144

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	353	355
Number [percentage of participants]	77.6 22%	74.6 21%

4. Secondary Outcome

Title	The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192
Time Frame	Week 192

Outcome Measure Data

Analysis Population Description

Week 192 modified intent-to-treat (MITT) Analysis Set: Participants in the ITT analysis set, excluding those who either 1) transferred to other Gilead-sponsored studies after completing their Week 144 Visit and before the lower limit of the Week 192 analysis window, or 2) prematurely discontinued study drug prior to the Week 144 Visit.

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	74	78
Number [percentage of participants]	78.4 22.2%	73.1 20.6%

5. Secondary Outcome

Title	The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT analysis set

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	353	355
Number [percentage of participants]	86.1 24.4%	84.8 23.9%

6. Secondary Outcome

Title	The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192
Description	Change = value of the relevant time point minus the baseline value
Time Frame	Baseline; Weeks 48, 96, 144, and 192

Outcome Measure Data

Analysis Population Description

ITT analysis set. The missing = excluded (M = E) method was used in which participants with missing data were excluded from analysis.

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	353	355
Change at Wk 48 (Stribild, n=334; ATV/r, n=321)	207 (164.2)	211 (160.3)
Change at Wk 96 (Stribild, n=317; ATV/r, n=315)	256 (166.8)	261 (188.0)
Change at Wk 144 (Stribild, n=297; ATV/r, n=286)	280 (159.8)	293 (211.5)
Change at Wk 192 (Stribild, n=69; ATV/r, n=72)	338 (186.8)	340 (224.2)

7. Secondary Outcome

Title	The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT analysis set. The missing = failure (M = F) method was used in which all missing data were considered as failure (HIV-1 RNA ≥ 50 copies/mL).

Arm/Group Title	Stribild	ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily	ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Measure Participants	353	355
Number [percentage of participants]	91.5 25.9%	88.5 24.9%

Adverse Events

Time Frame	Adverse events are reported for the double-blind treatment period of Stribild or ATV/r + Truvada up to 216 weeks plus 30 days.
Adverse Event Reporting Description	Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
Arm/Group Title	Stribild		ATV/r + FTC/TDF
Arm/Group Description	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily		ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
All Cause Mortality
	Stribild		ATV/r + FTC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stribild		ATV/r + FTC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/353 (16.4%)		62/355 (17.5%)
Blood and lymphatic system disorders
Thrombocytopenia	0/353 (0%)		1/355 (0.3%)
Cardiac disorders
Angina pectoris	0/353 (0%)		1/355 (0.3%)
Myocardial infarction	1/353 (0.3%)		2/355 (0.6%)
Congenital, familial and genetic disorders
Congenital ureteric anomaly	1/353 (0.3%)		0/355 (0%)
Eye disorders
Iridocyclitis	0/353 (0%)		1/355 (0.3%)
Gastrointestinal disorders
Abdominal pain	1/353 (0.3%)		4/355 (1.1%)
Colitis	1/353 (0.3%)		1/355 (0.3%)
Constipation	1/353 (0.3%)		0/355 (0%)
Diarrhoea	2/353 (0.6%)		0/355 (0%)
Diverticulum	1/353 (0.3%)		0/355 (0%)
Erosive oesophagitis	1/353 (0.3%)		0/355 (0%)
Gastritis erosive	0/353 (0%)		1/355 (0.3%)
Haemorrhoids	1/353 (0.3%)		0/355 (0%)
Intestinal obstruction	0/353 (0%)		1/355 (0.3%)
Large intestine perforation	0/353 (0%)		1/355 (0.3%)
Lower gastrointestinal haemorrhage	0/353 (0%)		1/355 (0.3%)
Pancreatitis	1/353 (0.3%)		0/355 (0%)
Peptic ulcer haemorrhage	0/353 (0%)		1/355 (0.3%)
Vomiting	0/353 (0%)		1/355 (0.3%)
General disorders
Asthenia	0/353 (0%)		1/355 (0.3%)
Chest pain	1/353 (0.3%)		1/355 (0.3%)
Pyrexia	1/353 (0.3%)		0/355 (0%)
Hepatobiliary disorders
Bile duct stone	0/353 (0%)		1/355 (0.3%)
Cholecystitis	0/353 (0%)		1/355 (0.3%)
Immune system disorders
Drug hypersensitivity	1/353 (0.3%)		0/355 (0%)
Infections and infestations
Abscess limb	0/353 (0%)		1/355 (0.3%)
Abscess neck	0/353 (0%)		1/355 (0.3%)
Anal abscess	1/353 (0.3%)		3/355 (0.8%)
Appendicitis	3/353 (0.8%)		1/355 (0.3%)
Appendicitis perforated	1/353 (0.3%)		0/355 (0%)
Arthritis infective	1/353 (0.3%)		0/355 (0%)
Breast abscess	1/353 (0.3%)		0/355 (0%)
Bronchitis	1/353 (0.3%)		0/355 (0%)
Bronchopneumonia	0/353 (0%)		1/355 (0.3%)
Cellulitis	1/353 (0.3%)		2/355 (0.6%)
Device related infection	0/353 (0%)		1/355 (0.3%)
Ear infection	0/353 (0%)		1/355 (0.3%)
Epididymitis	0/353 (0%)		1/355 (0.3%)
Gastroenteritis	0/353 (0%)		1/355 (0.3%)
Gastroenteritis cryptosporidial	1/353 (0.3%)		0/355 (0%)
Gastrointestinal infection	0/353 (0%)		1/355 (0.3%)
Herpes zoster oticus	0/353 (0%)		1/355 (0.3%)
Impetigo	0/353 (0%)		1/355 (0.3%)
Incision site infection	0/353 (0%)		1/355 (0.3%)
Infectious colitis	1/353 (0.3%)		0/355 (0%)
Influenza	1/353 (0.3%)		0/355 (0%)
Lymphogranuloma venereum	1/353 (0.3%)		0/355 (0%)
Malaria	1/353 (0.3%)		0/355 (0%)
Malignant syphilis	1/353 (0.3%)		0/355 (0%)
Meningitis aseptic	0/353 (0%)		1/355 (0.3%)
Meningitis enteroviral	0/353 (0%)		1/355 (0.3%)
Meningitis viral	0/353 (0%)		1/355 (0.3%)
Orchitis	0/353 (0%)		1/355 (0.3%)
Osteomyelitis	1/353 (0.3%)		1/355 (0.3%)
Peritonitis	2/353 (0.6%)		0/355 (0%)
Pilonidal cyst	0/353 (0%)		1/355 (0.3%)
Pneumocystis jirovecii pneumonia	0/353 (0%)		1/355 (0.3%)
Pneumonia	1/353 (0.3%)		1/355 (0.3%)
Pneumonia bacterial	1/353 (0.3%)		0/355 (0%)
Pneumonia streptococcal	1/353 (0.3%)		0/355 (0%)
Pyelonephritis acute	0/353 (0%)		1/355 (0.3%)
Respiratory syncytial virus infection	1/353 (0.3%)		0/355 (0%)
Salpingitis	1/353 (0.3%)		0/355 (0%)
Scrotal abscess	0/353 (0%)		1/355 (0.3%)
Secondary syphilis	1/353 (0.3%)		0/355 (0%)
Septic shock	0/353 (0%)		2/355 (0.6%)
Shigella infection	1/353 (0.3%)		0/355 (0%)
Staphylococcal infection	1/353 (0.3%)		0/355 (0%)
Tonsillitis	0/353 (0%)		1/355 (0.3%)
Urinary tract infection	1/353 (0.3%)		0/355 (0%)
Viral infection	1/353 (0.3%)		0/355 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/353 (0.3%)		0/355 (0%)
Ankle fracture	0/353 (0%)		1/355 (0.3%)
Clavicle fracture	1/353 (0.3%)		0/355 (0%)
Femur fracture	1/353 (0.3%)		0/355 (0%)
Hand fracture	0/353 (0%)		1/355 (0.3%)
Lower limb fracture	0/353 (0%)		1/355 (0.3%)
Lumbar vertebral fracture	1/353 (0.3%)		0/355 (0%)
Muscle rupture	1/353 (0.3%)		0/355 (0%)
Muscle strain	1/353 (0.3%)		0/355 (0%)
Overdose	2/353 (0.6%)		1/355 (0.3%)
Post concussion syndrome	1/353 (0.3%)		0/355 (0%)
Post procedural haemorrhage	0/353 (0%)		1/355 (0.3%)
Skull fractured base	1/353 (0.3%)		0/355 (0%)
Toxicity to various agents	1/353 (0.3%)		2/355 (0.6%)
Upper limb fracture	1/353 (0.3%)		1/355 (0.3%)
Wrist fracture	0/353 (0%)		1/355 (0.3%)
Investigations
Blood creatine phosphokinase increased	0/353 (0%)		1/355 (0.3%)
Metabolism and nutrition disorders
Dehydration	0/353 (0%)		1/355 (0.3%)
Hyperkalaemia	1/353 (0.3%)		0/355 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/353 (0%)		1/355 (0.3%)
Arthritis reactive	1/353 (0.3%)		0/355 (0%)
Foot deformity	0/353 (0%)		1/355 (0.3%)
Intervertebral disc displacement	0/353 (0%)		1/355 (0.3%)
Neck pain	0/353 (0%)		1/355 (0.3%)
Pain in jaw	0/353 (0%)		1/355 (0.3%)
Rhabdomyolysis	1/353 (0.3%)		1/355 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer	1/353 (0.3%)		1/355 (0.3%)
Anal squamous cell carcinoma	1/353 (0.3%)		0/355 (0%)
Anogenital warts	0/353 (0%)		1/355 (0.3%)
B-cell lymphoma stage II	0/353 (0%)		1/355 (0.3%)
Basal cell carcinoma	0/353 (0%)		1/355 (0.3%)
Bladder cancer	1/353 (0.3%)		0/355 (0%)
Bladder neoplasm	1/353 (0.3%)		0/355 (0%)
Burkitt's lymphoma	1/353 (0.3%)		0/355 (0%)
Hodgkin's disease	1/353 (0.3%)		1/355 (0.3%)
Nervous system disorders
Cervical radiculopathy	1/353 (0.3%)		0/355 (0%)
Coma	0/353 (0%)		1/355 (0.3%)
Convulsion	2/353 (0.6%)		0/355 (0%)
Critical illness polyneuropathy	0/353 (0%)		1/355 (0.3%)
Haemorrhage intracranial	1/353 (0.3%)		0/355 (0%)
Headache	0/353 (0%)		1/355 (0.3%)
Hypoaesthesia	0/353 (0%)		1/355 (0.3%)
Syncope	1/353 (0.3%)		1/355 (0.3%)
Tension headache	1/353 (0.3%)		0/355 (0%)
Transient ischaemic attack	1/353 (0.3%)		0/355 (0%)
VIIth nerve paralysis	0/353 (0%)		1/355 (0.3%)
Psychiatric disorders
Alcohol withdrawal syndrome	1/353 (0.3%)		1/355 (0.3%)
Bipolar disorder	0/353 (0%)		1/355 (0.3%)
Depressed mood	0/353 (0%)		1/355 (0.3%)
Depression	3/353 (0.8%)		1/355 (0.3%)
Depressive symptom	0/353 (0%)		1/355 (0.3%)
Drug dependence	1/353 (0.3%)		0/355 (0%)
Major depression	1/353 (0.3%)		0/355 (0%)
Mania	0/353 (0%)		1/355 (0.3%)
Post-traumatic stress disorder	1/353 (0.3%)		0/355 (0%)
Schizophrenia	1/353 (0.3%)		2/355 (0.6%)
Substance abuse	0/353 (0%)		1/355 (0.3%)
Substance-induced psychotic disorder	1/353 (0.3%)		0/355 (0%)
Suicidal ideation	2/353 (0.6%)		1/355 (0.3%)
Suicide attempt	2/353 (0.6%)		2/355 (0.6%)
Renal and urinary disorders
Hydronephrosis	1/353 (0.3%)		0/355 (0%)
Nephrolithiasis	1/353 (0.3%)		0/355 (0%)
Renal colic	0/353 (0%)		1/355 (0.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/353 (0.3%)		1/355 (0.3%)
Dyspnoea	1/353 (0.3%)		0/355 (0%)
Pneumonia aspiration	1/353 (0.3%)		1/355 (0.3%)
Respiratory depression	0/353 (0%)		1/355 (0.3%)
Respiratory distress	0/353 (0%)		1/355 (0.3%)
Tonsillar hypertrophy	1/353 (0.3%)		0/355 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	0/353 (0%)		1/355 (0.3%)
Psoriasis	0/353 (0%)		1/355 (0.3%)
Social circumstances
Treatment noncompliance	0/353 (0%)		1/355 (0.3%)
Vascular disorders
Orthostatic hypotension	0/353 (0%)		1/355 (0.3%)
Peripheral embolism	1/353 (0.3%)		0/355 (0%)
Thrombophlebitis	1/353 (0.3%)		0/355 (0%)
Venous thrombosis limb	1/353 (0.3%)		0/355 (0%)
Other (Not Including Serious) Adverse Events
	Stribild		ATV/r + FTC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	326/353 (92.4%)		326/355 (91.8%)
Blood and lymphatic system disorders
Lymphadenopathy	23/353 (6.5%)		16/355 (4.5%)
Eye disorders
Ocular icterus	2/353 (0.6%)		52/355 (14.6%)
Gastrointestinal disorders
Abdominal pain	25/353 (7.1%)		26/355 (7.3%)
Constipation	20/353 (5.7%)		14/355 (3.9%)
Diarrhoea	99/353 (28%)		121/355 (34.1%)
Dyspepsia	13/353 (3.7%)		19/355 (5.4%)
Flatulence	16/353 (4.5%)		32/355 (9%)
Nausea	80/353 (22.7%)		78/355 (22%)
Vomiting	26/353 (7.4%)		35/355 (9.9%)
General disorders
Fatigue	60/353 (17%)		60/355 (16.9%)
Pyrexia	23/353 (6.5%)		22/355 (6.2%)
Hepatobiliary disorders
Jaundice	0/353 (0%)		34/355 (9.6%)
Immune system disorders
Seasonal allergy	17/353 (4.8%)		19/355 (5.4%)
Infections and infestations
Bronchitis	47/353 (13.3%)		42/355 (11.8%)
Chlamydial infection	18/353 (5.1%)		17/355 (4.8%)
Folliculitis	19/353 (5.4%)		22/355 (6.2%)
Gastroenteritis	18/353 (5.1%)		28/355 (7.9%)
Herpes zoster	15/353 (4.2%)		20/355 (5.6%)
Influenza	31/353 (8.8%)		24/355 (6.8%)
Nasopharyngitis	53/353 (15%)		57/355 (16.1%)
Onychomycosis	21/353 (5.9%)		13/355 (3.7%)
Pharyngitis	23/353 (6.5%)		18/355 (5.1%)
Sinusitis	35/353 (9.9%)		38/355 (10.7%)
Syphilis	27/353 (7.6%)		29/355 (8.2%)
Upper respiratory tract infection	86/353 (24.4%)		97/355 (27.3%)
Urinary tract infection	18/353 (5.1%)		20/355 (5.6%)
Metabolism and nutrition disorders
Decreased appetite	14/353 (4%)		19/355 (5.4%)
Vitamin D deficiency	21/353 (5.9%)		19/355 (5.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	35/353 (9.9%)		32/355 (9%)
Back pain	46/353 (13%)		37/355 (10.4%)
Pain in extremity	22/353 (6.2%)		21/355 (5.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anorectal human papilloma virus infection	21/353 (5.9%)		12/355 (3.4%)
Nervous system disorders
Dizziness	25/353 (7.1%)		28/355 (7.9%)
Headache	67/353 (19%)		55/355 (15.5%)
Paraesthesia	9/353 (2.5%)		21/355 (5.9%)
Psychiatric disorders
Anxiety	22/353 (6.2%)		29/355 (8.2%)
Depression	47/353 (13.3%)		52/355 (14.6%)
Insomnia	37/353 (10.5%)		36/355 (10.1%)
Respiratory, thoracic and mediastinal disorders
Cough	38/353 (10.8%)		46/355 (13%)
Oropharyngeal pain	19/353 (5.4%)		32/355 (9%)
Skin and subcutaneous tissue disorders
Night sweats	10/353 (2.8%)		18/355 (5.1%)
Rash	30/353 (8.5%)		37/355 (10.4%)
Vascular disorders
Hypertension	24/353 (6.8%)		12/355 (3.4%)

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