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Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Fixed Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Positive Participants

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01815736
Collaborator
(none)
1,443
Enrollment
167
Locations
2
Arms
84.2
Actual Duration (Months)
8.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the non-inferiority of switching to a tenofovir alafenamide (TAF)-containing fixed dose combination (FDC) relative to maintaining tenofovir disoproxil fumarate (TDF)-containing combination regimens in virologically suppressed HIV-infected participants as determined by having HIV-1 RNA < 50 copies/mL at Week 48.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1443 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 a TDF-Containing Combination Regimen to a TAF-Containing Combination Single Tablet Regimen (STR) in Virologically-Suppressed, HIV-1 Positive Subjects
Actual Study Start Date :
Mar 27, 2013
Actual Primary Completion Date :
Mar 16, 2015
Actual Study Completion Date :
Apr 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: E/C/F/TAF

Randomized Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment, all participants will be given the opportunity to receive open-label E/C/F/TAF until it becomes commercially available, or until Gilead elects to terminate the development of E/C/F/TAF.

Drug: E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily
Other Names:
  • EVG/COBI/FTC/TAF; Genvoya®

    		•
    Active Comparator: Stay on Baseline Treatment Regimen (SBR)

    Randomized Phase: Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF) administered according to prescribing information for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment (SBR), all participants will be given the opportunity to receive open-label E/C/F/TAF until it becomes commercially available, or until Gilead elects to terminate the development of E/C/F/TAF.

    Drug: E/C/F/TDF
    150/150/200/300 mg FDC tablet administered orally once daily
    Other Names:
  • Stribild®

    • Drug: EFV/FTC/TDF
    600/200/300 mg FDC tablet administered orally once daily
    Other Names:
  • Atripla®

    • Drug: RTV
    100 mg tablet administered orally once daily
    Other Names:
  • Norvir®

    • Drug: ATV
    300 mg capsule administered orally once daily
    Other Names:
  • Reyataz®

    • Drug: FTC/TDF
    200/300 mg tablet administered orally once daily
    Other Names:
  • Truvada®

    • Drug: COBI
    150 mg tablet administered orally once daily
    Other Names:
  • Tybost®
  • GS-9350

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants 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.

    Secondary Outcome Measures

    1. Percent 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. BMD is calculated as grams per square centimeter (g/cm^2); the mean (SD) percentage change is presented.

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

      Spine BMD was assessed by DXA scan. BMD is calculated as g/cm^2; the mean (SD) percentage change is presented.

    3. Change From Baseline in Serum Creatinine at Week 48 [Baseline; Week 48]

    4. Change From Baseline in the Overall EFV-related Symptom Assessment Score at Week 48 [Baseline; Week 48]

      The mean (SD) change of the overall EFV-related symptom assessment score is presented. The overall symptom score (ranging from 0 to 20) is the sum of the individual symptom scores ranging from 0 (no symptoms) to 4 (most severe symptoms) from the 5 EFV-related symptom assessments (dizziness, trouble sleeping, impaired concentration, sleepiness, and abnormal or vivid dream). A negative change from baseline indicates improvement. EFV-Related Symptom Analysis Set: participants who received EFV/FTC/TDF as prior treatment, received at least 1 dose of study drug, and completed EFV-related symptom assessments at the baseline visit and at least 1 postbaseline visit.

    5. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [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 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.

    6. Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 [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 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.

    7. Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 [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 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.

    8. Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48 [Baseline; Week 48]

      The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen.

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

      The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen.

    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 therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study

    • Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105

    • Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA < 50 copies/mL at the screening visit

    • Normal echocardiograph (ECG)

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

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

    • Direct bilirubin ≤ 1.5 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 sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.

    • Female participants 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

    • Female participants 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

    Key Exclusion Criteria:

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

    • Hepatitis B surface antigen position

    • Hepatitis C antibody positive

    • Participants experiencing decompensated cirrhosis

    • 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 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

    • 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 dosing requirements

    • Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial

    • Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF

    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 Southwest Center for HIV/AIDS Phoenix Arizona United States 85006
    3 Spectrum Medical Group Phoenix Arizona United States 85012
    4 Health for Life Clinic PLLC Little Rock Arkansas United States 72207
    5 AHF Research Center Beverly Hills California United States 90211
    6 Michael Keith Wensley, MD, Inc., A Medical Corporation Costa Mesa California United States 92626
    7 Living Hope Clinical Foundation Long Beach California United States 90813
    8 Kaiser Permanente Los Angeles California United States 90027
    9 Jeffrey Goodman Special Care Clinic Los Angeles California United States 90028
    10 Peter J Ruane, MD, Inc Los Angeles California United States 90036
    11 Anthony Mills MD Inc Los Angeles California United States 90069
    12 Orange Coast Medical Group Newport Beach California United States 92663
    13 Alameda County Medical Center Oakland California United States 94602
    14 East Bay AIDS Center Oakland California United States 94609
    15 Stanford University Palo Alto California United States 94303
    16 University of California, Davis Medical Center Sacramento California United States 95817
    17 Kaiser Permanente Medical Group Sacramento California United States 95825
    18 La Playa Medical Group and Clinical Research San Diego California United States 92103
    19 Metropolis Medical Group San Francisco California United States 94109
    20 Kaiser Permanente Medical Center, Clinical Trials Unit San Francisco California United States 94118
    21 Kaiser Permanente Hospital San Leandro California United States 94577
    22 Apex Research LLC Denver Colorado United States 80209
    23 Greenwich Hospital Greenwich Connecticut United States 06830
    24 Yale University HIV Clinical Trials Program New Haven Connecticut United States 06510
    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/ Value Health MD, 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 AIDS Research Consortium of Atlanta Atlanta Georgia United States 30308
    41 Atlanta ID Group, PC Atlanta Georgia United States 30309
    42 Infectious Disease Specialists of Atlanta Decatur Georgia United States 30033
    43 Mercer University School of Medicine Macon Georgia United States 31201
    44 University of Hawaii - Hawaii Center for AIDS 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 NorthStar Medical Center Chicago Illinois United States 60657
    48 Community Research Initiative of New England Boston Massachusetts United States 02111
    49 The Research Institute Springfield Massachusetts United States 01105
    50 Baystate Infectious Diseases Clinical Research Springfield Massachusetts United States 01199
    51 Be Well Medical Center Berkley Michigan United States 48072
    52 Henry Ford Health System Detroit Michigan United States 48202
    53 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    54 Central West Clinical Research Saint Louis Missouri United States 63108
    55 Saint Louis University Saint Louis Missouri United States 63110
    56 Southampton Healthcare Saint Louis Missouri United States 63139
    57 ID Care Hillsborough New Jersey United States 08844
    58 Saint Michaels Medical Center Newark New Jersey United States 07102
    59 South Jersey Infectious Disease Somers Point New Jersey United States 08244
    60 SouthWest CARE Center Santa Fe New Mexico United States 87505
    61 Upstate ID Association Albany New York United States 12208
    62 Albany Medical College Albany New York United States 12209
    63 Jacobi Medical Center Bronx New York United States 10461
    64 Montefiore Medical Center - AIDS Center Bronx New York United States 10467
    65 New York Hospital Queens Flushing New York United States 11355
    66 North Shore University Hospital, Divison of Infectious Diseases Manhasset New York United States 11030
    67 Greiger Clinic Mount Vernon New York United States 10550
    68 Beth Israel Medical Center- Division of Infectious Diseases New York New York United States 10003
    69 Chelsea Village Medical, PC New York New York United States 10011
    70 Ricky K. Hsu, MD New York New York United States 10011
    71 University of NC AIDS Clinical Trials Unit Chapel Hill North Carolina United States 27599
    72 Carolinas Medical Center-Myers Park Charlotte North Carolina United States 28207
    73 Duke University Health System Durham North Carolina United States 27710
    74 East Carolina University Greenville North Carolina United States 27834
    75 Rosedale Infectious Diseases Huntersville North Carolina United States 28078
    76 Summa Health System Akron Ohio United States 44304
    77 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    78 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    79 Palmetto Health Richland Columbia South Carolina United States 29203
    80 AIDS Arms, Inc./ Peabody Health Center Dallas Texas United States 75215
    81 Southwest Infectious Disease Clinical Research, Inc. Dallas Texas United States 75219
    82 Tarrant County Infectious Disease Associates Fort Worth Texas United States 76104
    83 Garcia's Family Health Group Harlingen Texas United States 78550
    84 Therapeutic Concepts, P.A. Houston Texas United States 77004
    85 Gordon E. Crofoot MD PA Houston Texas United States 77098
    86 Research Access Network Houston Texas United States 77098
    87 DCOL Center for Clinical Research Longview Texas United States 75605
    88 Clinical Alliance for Research & Education, Infectious Diseases (CARE-ID) Annandale Virginia United States 22003
    89 Peter Shalit, M.D. Seattle Washington United States 98104
    90 Premier Clinical Research Spokane Washington United States 99202
    91 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    92 East Sydney Doctors Darlinghurst New South Wales Australia 2010
    93 Holdsworth House Medical practice Darlinghurst New South Wales Australia 2010
    94 St Vincent's Hospital, Sydney Darlinghurst New South Wales Australia 2010
    95 Taylor Square Private Clinic Darlinghurst New South Wales Australia 2010
    96 Albion Street Centre Surry Hills New South Wales Australia 2010
    97 Melbourne Sexual Health Clinic Carlton Victoria Australia 3053
    98 Alfred Hospital Melbourne Victoria Australia 3004
    99 Northside Clinic Melbourne Victoria Australia 3068
    100 Prahran Market Clinic South Yarra Victoria Australia 3141
    101 Medizinische Universität Graz Graz Austria 8020
    102 Medizinische Universitat Wien Vienna Austria 1090
    103 SMZ Baumgartner Hoehe - Otto-Wagner-Spital Vienna Austria 1140
    104 CHU Saint-Pierre University Hospital Brussels Belgium 1000
    105 Hôpital Universitaire Erasme - ULB Ghent Belgium 1070
    106 Instituto De Pesquisa Clinica Evandro Chagas - Fundação Oswaldo Cruz Rio de Janeiro Brazil 21040-360
    107 Faculdade de Medicina do ABC Santo Andre Brazil 09060-650
    108 São Paulo Secretaria da Saúde - Instituto De Infectologia Emilio Ribas Sao Paulo Brazil 01246-900
    109 São Paulo Secretaria da Saúde - Centro de Referência e Treinamento em DST/AIDS Sao Paulo Brazil 04121-000
    110 Ubc Downtown I.D. Clinic Vancouver British Columbia Canada V6Z 2C7
    111 Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg Winnipeg Manitoba Canada R3A 1R9
    112 Ottawa Hospital Ottawa Ontario Canada K1H 8L6
    113 Sunnybrook Health Sciences Centre Toronto Ontario Canada M4N 3M5
    114 Maple Leaf Research Toronto Ontario Canada M5G 1K2
    115 University Health Network, Toronto General Hospital Toronto Ontario Canada M5G 2N2
    116 Clinique medicale l'Actuel Montreal Quebec Canada H2L 4P9
    117 Clinique Medicale du Quartier Latin Montreal Quebec Canada H2L 5B1
    118 Clinique OPUS Montreal Quebec Canada H3A 1T1
    119 McGill University Health Centre (MUHC) - Montral Chest Institute Montréal Quebec Canada H2X 2P4
    120 Epidemiklinikken 5112, Rigshospitalet Copenhagen Denmark 2100
    121 Instituto Dominicano de Estudios Virologicos - IDEV Santo Domingo Dominican Republic
    122 Hôpital de La Croix Rousse Lyon France 75970
    123 CHU Hotel Dieu Nantes France 44093
    124 Archet 1 CHU de Nice - 6ème Niveau Nice France 06200
    125 Hôpital Saint Louis Paris France 75010
    126 Hopital Saint Antoine Paris France 75012
    127 Bichat Hospital Paris France 75018
    128 Centre Hospitalier de Tourcoing Tourcoing France 59208
    129 EPIMED GmbH Berlin Germany 12157
    130 University of Bonn Bonn Germany 53127
    131 Center for HIV and Hepatogastroenterology Duesseldorf Germany 40237
    132 Infektio Research GmbH / Infektiologikum Frankfurt Frankfurt am Main Germany 60311
    133 Universitätsklinikum Frankfurt Frankfurt am Main Germany 60590
    134 Universitatsklinikum Freiburg Freiburg Germany 79106
    135 ICH Study Center Hamburg Hamburg Germany 20146
    136 University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit Hamburg Germany 20246
    137 University of Cologne, Department of Internal Medicine Köln Germany 50937
    138 MUC Research GmbH München Germany 80335
    139 Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive Milano Italy 20157
    140 Fondazione Centro San Raffaele del Monte Tabor Milan Italy 20127
    141 Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS Rome Italy 00149
    142 Comprensorio Amedeo Di Savoia Birago Di Vische Torino Italy 10149
    143 Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde" Guadalajara Mexico 44280
    144 Onze Lieve Vrouwe Gasthuis, Afdeling Infectieziekten Amsterdam Netherlands 1091 AC
    145 Erasmus MC Rotterdam Netherlands 3000 CA
    146 Hospital de Santa Maria Lisbon Portugal 1649-035
    147 Servico De Doencas Infecciosas - Hospital De Sao Joao Porto Portugal 4202-451
    148 Clinical Research Puerto Rico San Juan Puerto Rico 00909
    149 HOPE Clinical Research San Juan Puerto Rico 00909
    150 VA Caribbean Healthcare System San Juan Puerto Rico 00921
    151 Hospital Universitari De Bellvitge Barcelona Spain 08907
    152 Hospital Universitario La Paz Madrid Spain 28046
    153 Hospital Virgen del Rocio Sevilla Spain 41013
    154 Södersjukhuset Stockholm Sweden 11883
    155 Universitätsklinik für Infektiologie, Universitätsspital Bern Bern Switzerland 3010
    156 Centre Hospitalier Universitaire Vaudois Lausanne Switzerland 1011
    157 University Hospital of Zurich Zürich Switzerland 8091
    158 HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine Chulalongkorn University Bangkok Thailand 10330
    159 Ramathibodi Hospital, Mahidol University Bangkok Thailand 10400
    160 Siriraj HospitalDepartment of Preventive and Social Medicine, Faculty of Medicine Bangkok Thailand 10700
    161 Maharaj Nakorn Chiang Mai University, Faculty of Medicine, Department of Medicine Chiang Mai Thailand 50200
    162 Khon Kaen University Khon Kaen Thailand 40002
    163 Brighton and Sussex University Hospitals NHS Trust Brighton United Kingdom BN2 1ES
    164 Barts and the London NHS Trust London United Kingdom E1 1BB
    165 Chelsea and Westminster Hospital Foundation Trust London United Kingdom SW10 9NH
    166 Courtyard Clinic, St. Georges Hospital London United Kingdom SW17 0QT
    167 North Manchester General Hospital Manchester United Kingdom M8 5RB

    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:
    NCT01815736
    Other Study ID Numbers:
    • GS-US-292-0109
    • 2012-005114-20
    First Posted:
    Mar 21, 2013
    Last Update Posted:
    Apr 13, 2021
    Last Verified:
    Mar 1, 2021
    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 Infected
    Virologically-Suppressed
    Additional relevant MeSH terms:
    HIV Infections
    Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in Dominican Republic, Puerto Rico, North America, South America, Europe, Australia, and Asia. The first participant was screened on 27 March 2013. The last study visit occurred on 01 April 2020.
    Pre-assignment Detail 1559 participants were screened.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Randomized Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet administered once daily for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment, all participants were given the opportunity to receive open-label E/C/F/TAF until it became commercially available, or until Gilead elected to terminate the development of E/C/F/TAF. Randomized Phase: Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment (SBR), all participants were given the opportunity to receive open-label E/C/F/TAF until it became commercially available, or until Gilead elected to terminate the development of E/C/F/TAF.
    Period Title: Randomized Treatment Phase-Up to Week 96
    STARTED 963 480
    COMPLETED 914 445
    NOT COMPLETED 49 35
    Period Title: Randomized Treatment Phase-Up to Week 96
    STARTED 905 424
    COMPLETED 854 398
    NOT COMPLETED 51 26

    Baseline Characteristics

    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR) Total
    Arm/Group Description Randomized Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)(150/150/200/10 mg) fixed-dose combination (FDC) tablet administered once daily for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment, all participants were given the opportunity to receive open-label E/C/F/TAF until it became commercially available, or until Gilead elected to terminate the development of E/C/F/TAF. Randomized Phase: Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment (SBR), all participants were given the opportunity to receive open-label E/C/F/TAF until it became commercially available, or until Gilead elected to terminate the development of E/C/F/TAF. Total of all reporting groups
    Overall Participants 959 477 1436
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    41
    (10.1)
    41
    (10.1)
    41
    (10.1)
    Sex: Female, Male (Count of Participants)
    Female
    103
    10.7%
    50
    10.5%
    153
    10.7%
    Male
    856
    89.3%
    427
    89.5%
    1283
    89.3%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    5
    0.5%
    2
    0.4%
    7
    0.5%
    Asian
    59
    6.2%
    35
    7.3%
    94
    6.5%
    Black
    169
    17.6%
    102
    21.4%
    271
    18.9%
    Native Hawaiian or Pacific Islander
    6
    0.6%
    1
    0.2%
    7
    0.5%
    White
    651
    67.9%
    314
    65.8%
    965
    67.2%
    Local regulators did not allow collection of race or ethnicity information
    2
    0.2%
    1
    0.2%
    3
    0.2%
    Other
    67
    7%
    22
    4.6%
    89
    6.2%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    248
    25.9%
    82
    17.2%
    330
    23%
    Not Hispanic or Latino
    709
    73.9%
    392
    82.2%
    1101
    76.7%
    Local regulators did not allow collection of race or ethnicity information
    2
    0.2%
    3
    0.6%
    5
    0.3%
    Region of Enrollment (participants) [Number]
    United States
    648
    67.6%
    316
    66.2%
    964
    67.1%
    United Kingdom
    14
    1.5%
    8
    1.7%
    22
    1.5%
    Thailand
    35
    3.6%
    21
    4.4%
    56
    3.9%
    Portugal
    8
    0.8%
    2
    0.4%
    10
    0.7%
    Switzerland
    5
    0.5%
    4
    0.8%
    9
    0.6%
    Spain
    5
    0.5%
    3
    0.6%
    8
    0.6%
    Canada
    51
    5.3%
    27
    5.7%
    78
    5.4%
    Austria
    16
    1.7%
    8
    1.7%
    24
    1.7%
    Netherlands
    2
    0.2%
    3
    0.6%
    5
    0.3%
    Sweden
    1
    0.1%
    0
    0%
    1
    0.1%
    Belgium
    14
    1.5%
    8
    1.7%
    22
    1.5%
    Brazil
    14
    1.5%
    5
    1%
    19
    1.3%
    Denmark
    1
    0.1%
    2
    0.4%
    3
    0.2%
    Dominican Republic
    29
    3%
    13
    2.7%
    42
    2.9%
    Italy
    13
    1.4%
    6
    1.3%
    19
    1.3%
    Mexico
    19
    2%
    6
    1.3%
    25
    1.7%
    Australia
    38
    4%
    22
    4.6%
    60
    4.2%
    France
    12
    1.3%
    12
    2.5%
    24
    1.7%
    Germany
    34
    3.5%
    11
    2.3%
    45
    3.1%
    HIV-1 RNA Category (Count of Participants)
    < 50 copies/mL
    943
    98.3%
    466
    97.7%
    1409
    98.1%
    ≥ 50 copies/mL
    16
    1.7%
    11
    2.3%
    27
    1.9%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants 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 were randomized and received at least 1 dose of study drug. New Drug Application (NDA Data Cut) = participants through the data cut for the E/C/F/TAF NDA; All Participants = participants through the Week 48 Data Cut.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 959 477
    NDA Data Cut
    95.6
    10%
    92.9
    19.5%
    All Participants
    97.2
    10.1%
    93.1
    19.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Null hypothesis: the E/C/F/TAF group was at least 12% worse than the Stay on Baseline Regimen group; alternative hypothesis: the E/C/F/TAF group was less than 12% worse than the in Stay on Baseline Regimen group.
    Statistical Test of Hypothesis p-Value 0.051
    Comments The p-value for the superiority test used a 2-sided Cochran-Mantel-Haenszel (CMH) test, stratified by prior treatment regimen.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 2.7
    Confidence Interval (2-Sided) 95.01%
    -0.3 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in percentages and its 95.01% confidence interval (CI) were calculated based on the Mantel-Haenszel (MH) proportion adjusted by the prior treatment regimen.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Null hypothesis: the E/C/F/TAF group was at least 12% worse than the Stay on Baseline Regimen group; alternative hypothesis: the E/C/F/TAF group was less than 12% worse than the in Stay on Baseline Regimen group.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The p-value for the superiority test used a 2-sided Cochran-Mantel-Haenszel (CMH) test, stratified by prior treatment regimen.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 4.1
    Confidence Interval (2-Sided) 95%
    1.6 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in percentages and its 95% confidence interval (CI) were calculated based on the Mantel-Haenszel (MH) proportion adjusted by the prior treatment regimen.
    2. Secondary Outcome
    Title Percent 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. BMD is calculated as grams per square centimeter (g/cm^2); the mean (SD) percentage change is presented.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Hip DXA Analysis Set (participants who received ≥ 1 dose of study drug and had nonmissing baseline hip BMD) with available data were analyzed. NDA Data Cut = participants through the data cut for the E/C/F/TAF NDA; All Participants = participants through the Week 48 Data Cut.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 902 452
    NDA Data Cut
    1.949
    (2.9956)
    -0.136
    (2.9890)
    All Participants
    1.468
    (2.7136)
    -0.340
    (2.8280)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value was from the analysis of variance (ANOVA) model including study treatment and prior treatment regimen as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least square means
    Estimated Value 2.078
    Confidence Interval (2-Sided) 95%
    1.697 to 2.459
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means (LSM) and its 95% CI were from the ANOVA model including treatment and prior treatment regimen as fixed effects.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value was from the analysis of variance (ANOVA) model including study treatment and prior treatment regimen as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least square means
    Estimated Value 1.807
    Confidence Interval (2-Sided) 95%
    1.488 to 2.126
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means and its 95% CI were from the ANOVA model including treatment and prior treatment regimen as fixed effects.
    3. Secondary Outcome
    Title Percent Change From Baseline in Spine BMD at Week 48
    Description Spine BMD was assessed by DXA scan. BMD is calculated as g/cm^2; the mean (SD) percentage change is presented.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Spine DXA Analysis Set (participants who received ≥ 1 dose of study drug and had nonmissing baseline spine BMD) with available data were analyzed. NDA Data Cut = participants through the data cut for the E/C/F/TAF NDA; All Participants = participants through the Week 48 Data Cut.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 912 457
    NDA Data Cut
    1.861
    (3.0889)
    -0.110
    (3.7415)
    All Participants
    1.557
    (3.8441)
    -0.443
    (4.1387)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value was from the analysis of variance (ANOVA) model including study treatment and prior treatment regimen as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least square means
    Estimated Value 1.970
    Confidence Interval (2-Sided) 95%
    1.551 to 2.390
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means (LSM) and its 95% CI were from the ANOVA model including treatment and prior treatment regimen as fixed effects.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value was from the analysis of variance (ANOVA) model including study treatment and prior treatment regimen as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least square means
    Estimated Value 2.000
    Confidence Interval (2-Sided) 95%
    1.549 to 2.452
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means (LSM) and its 95% CI were from the ANOVA model including treatment and prior treatment regimen as fixed effects.
    4. Secondary Outcome
    Title Change From Baseline in Serum Creatinine at Week 48
    Description
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set (randomized participants who received ≥ 1 dose of study drug) excluding participants with prior treatment of EFV/FTC/TDF. NDA Data Cut = participants through the data cut for the E/C/F/TAF NDA; All Participants = participants through the Week 48 Data Cut
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 708 352
    NDA Data Cut
    -0.01
    (0.117)
    0.04
    (0.123)
    All Participants
    0.00
    (0.115)
    0.03
    (0.105)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value was from analysis of covariance (ANCOVA) model including study treatment and prior treatment as fixed effects and baseline serum creatinine as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least square means
    Estimated Value -0.05
    Confidence Interval (2-Sided) 95%
    -0.07 to -0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means (LSM) and its 95% CI were from the analysis of covariance (ANCOVA) model including study treatment and prior treatment regimen as fixed effects and baseline serum creatinine as a covariate.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value was from analysis of covariance (ANCOVA) model including study treatment and prior treatment as fixed effects and baseline serum creatinine as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least square means
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -0.05 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means (LSM) and its 95% CI were from the analysis of covariance (ANCOVA) model including study treatment and prior treatment regimen as fixed effects and baseline serum creatinine as a covariate.
    5. Secondary Outcome
    Title Change From Baseline in the Overall EFV-related Symptom Assessment Score at Week 48
    Description The mean (SD) change of the overall EFV-related symptom assessment score is presented. The overall symptom score (ranging from 0 to 20) is the sum of the individual symptom scores ranging from 0 (no symptoms) to 4 (most severe symptoms) from the 5 EFV-related symptom assessments (dizziness, trouble sleeping, impaired concentration, sleepiness, and abnormal or vivid dream). A negative change from baseline indicates improvement. EFV-Related Symptom Analysis Set: participants who received EFV/FTC/TDF as prior treatment, received at least 1 dose of study drug, and completed EFV-related symptom assessments at the baseline visit and at least 1 postbaseline visit.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in EFV-Related Symptom Analysis Set with available data were analyzed. NDA Data Cut = participants through data cut for E/C/F/TAF NDA; All Participants = participants through Week 48 Data Cut
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 239 116
    NDA Data Cut
    -1.6
    (3.06)
    -0.1
    (2.43)
    All Participants
    -1.5
    (3.06)
    -0.1
    (2.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The P-value comparing the 2 treatment groups was from the 2-sided Wilcoxon rank sum test.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The P-value comparing the 2 treatment groups was from the 2-sided Wilcoxon rank sum test.
    Method Wilcoxon (Mann-Whitney)
    Comments
    6. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
    Description The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 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 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 959 477
    Number [percentage of participants]
    92.8
    9.7%
    89.1
    18.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Null hypothesis: The E/C/F/TAF group was at least 12% worse than the Stay on Baseline Regimen group; alternative hypothesis: the E/C/F/TAF group was less than 12% worse than the in Stay on Baseline Regimen group.
    Statistical Test of Hypothesis p-Value 0.017
    Comments P-value for the superiority test comparing the percentages of virologic success was from the CMH test stratified by the prior treatment regimen (STB, ATR, ATV/boosted+TVD).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 3.7
    Confidence Interval (2-Sided) 95%
    0.4 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference in percentages of virologic success and its 95% CI were calculated based on the MH proportion adjusted by the prior treatment regimen.
    7. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48
    Description The percentage of participants achieving HIV-1 RNA < 20 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
    Participants in the Full Analysis Set were analyzed. NDA Data Cut = participants through the data cut for the E/C/F/TAF NDA; All Participants = participants through the Week 48 Data Cut.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 959 477
    NDA Data Cut
    92.2
    9.6%
    90.4
    19%
    All Participants
    93.5
    9.7%
    90.4
    19%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Null hypothesis: The E/C/F/TAF group was at least 12% worse than the Stay on Baseline Regimen group; alternative hypothesis: the E/C/F/TAF group was less than 12% worse than the in Stay on Baseline Regimen group.
    Statistical Test of Hypothesis p-Value 0.29
    Comments P-value for the superiority test comparing the percentages of virologic success was from the CMH test stratified by the prior treatment regimen (STB, ATR, ATV/boosted+TVD).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    -1.7 to 5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in percentages of virologic success and its 95% CI were calculated based on the MH proportion adjusted by the prior treatment regimen.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Null hypothesis: the E/C/F/TAF group was at least 12% worse than the Stay on Baseline Regimen group; alternative hypothesis: the E/C/F/TAF group was less than 12% worse than the in Stay on Baseline Regimen group.
    Statistical Test of Hypothesis p-Value 0.031
    Comments P-value for the superiority test comparing the percentages of virologic success was from the CMH test stratified by the prior treatment regimen (STB, ATR, ATV/boosted+TVD).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 3.2
    Confidence Interval (2-Sided) 95%
    0.1 to 6.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in percentages of virologic success and its 95% CI were calculated based on the MH proportion adjusted by the prior treatment regimen.
    8. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96
    Description The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 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 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 959 477
    Number [percentage of participants]
    90.6
    9.4%
    85.3
    17.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Null hypothesis: the E/C/F/TAF group was at least 12% worse than the Stay on Baseline Regimen group; alternative hypothesis: the E/C/F/TAF group was less than 12% worse than the in Stay on Baseline Regimen group.
    Statistical Test of Hypothesis p-Value 0.003
    Comments P-value for the superiority test comparing the percentages of virologic success was from the CMH test stratified by the prior treatment regimen (STB, ATR, ATV/boosted+TVD).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 5.3
    Confidence Interval (2-Sided) 95%
    1.6 to 9.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in percentages of virologic success and its 95% CI were calculated based on the MH proportion adjusted by the prior treatment regimen.
    9. Secondary Outcome
    Title Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48
    Description The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed. NDA Data Cut = participants through the data cut for the E/C/F/TAF NDA; All Participants = participants through the Week 48 Data Cut.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 959 477
    Baseline (NDA Data Cut)
    712
    (267.9)
    690
    (251.4)
    Change at Week 48 (NDA Data Cut)
    33
    (166.6)
    27
    (160.2)
    Baseline (All Participants)
    701
    (261.8)
    689
    (248.0)
    Change at Week 48 (All Participants)
    35
    (164.6)
    24
    (156.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments NDA Data Cut: Change at Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.56
    Comments P-values were from the analysis of variance (ANOVA) model including treatment (E/C/F/TAF vs. SBR) and prior treatment regimen (STB, ATR, ATV/boosted+TVD) as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least squares means
    Estimated Value 6
    Confidence Interval (2-Sided) 95%
    -14 to 26
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means (Diff in LSM), and its 95% CI were from the analysis of variance (ANOVA) model including treatment (E/C/F/TAF vs. FTC/TDF+3rd Agent) and prior treatment regimen (STB, ATR, ATV/boosted+TVD) as fixed effects.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments All Participants: Change at Week 48
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.26
    Comments P-values were from the analysis of variance (ANOVA) model including treatment (E/C/F/TAF vs. SBR) and prior treatment regimen (STB, ATR, ATV/boosted+TVD) as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least squares means
    Estimated Value 11
    Confidence Interval (2-Sided) 95%
    -8 to 29
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means and its 95% CI were from the analysis of variance (ANOVA) model including treatment (E/C/F/TAF vs.SBR) and prior treatment regimen (STB, ATR, ATV/boosted+TVD) as fixed effects.
    10. Secondary Outcome
    Title Change From Baseline in CD4 Cell Count at Weeks 96
    Description The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen.
    Time Frame Baseline; Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title E/C/F/TAF Stay on Baseline Treatment Regimen (SBR)
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen (E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF)) administered according to prescribing information for up to 96 weeks in the Randomized Phase.
    Measure Participants 959 477
    Baseline
    701
    (261.8)
    689
    (248.0)
    Change at Week 96
    60
    (181.6)
    42
    (158.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection E/C/F/TAF, Stay on Baseline Treatment Regimen (SBR)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.074
    Comments P-values were from the analysis of variance (ANOVA) model including treatment (E/C/F/TAF vs. SBR) and prior treatment regimen (STB, ATR, ATV/boosted+TVD) as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least squares means
    Estimated Value 18
    Confidence Interval (2-Sided) 95%
    -2 to 38
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in least squares means and its 95% CI were from the analysis of variance (ANOVA) model including treatment (E/C/F/TAF vs. SBR) and prior treatment regimen (STB, ATR, ATV/boosted+TVD) as fixed effects.

    Adverse Events

    Time Frame From the first dose date up to last dose date ( maximum: 307.7 weeks) plus 30 days
    Adverse Event Reporting Description Safety Analysis Set included participants who were randomized and received at least one dose of study drug. For All Cause Mortality: All Randomized Analysis Set included all participants who were randomized into the study.
    Arm/Group Title Randomized Phase: E/C/F/TAF Randomized Phase: Stay on Baseline Treatment Regimen (SBR) Extension Phase: E/C/F/TAF From E/C/F/TAF Extension Phase: E/C/F/TAF From SBR
    Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; EVG/COBI/FTC/TAF; E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered once daily for up to 96 weeks in the Randomized Phase. Participants stayed on their baseline emtricitabine(FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen E/C/F/TDF (Stribild®); efavirenz (EFV)/FTC/TDF (Atripla®); ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF) administered according to prescribing information for up to 96 weeks in the Randomized Phase. After completing 96 weeks of randomized treatment (E/C/F/TAF), all participants were given the opportunity to receive open-label E/C/F/TAF in the extension phase until it became commercially available, or until Gilead elected to terminate the development of E/C/F/TAF. After completing 96 weeks of randomized treatment (SBR), all participants were given the opportunity to receive open-label E/C/F/TAF in the extension phase until it became commercially available, or until Gilead elected to terminate the development of E/C/F/TAF.
    All Cause Mortality
    Randomized Phase: E/C/F/TAF Randomized Phase: Stay on Baseline Treatment Regimen (SBR) Extension Phase: E/C/F/TAF From E/C/F/TAF Extension Phase: E/C/F/TAF From SBR
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/963 (0.4%) 0/480 (0%) 1/905 (0.1%) 1/424 (0.2%)
    Serious Adverse Events
    Randomized Phase: E/C/F/TAF Randomized Phase: Stay on Baseline Treatment Regimen (SBR) Extension Phase: E/C/F/TAF From E/C/F/TAF Extension Phase: E/C/F/TAF From SBR
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 79/959 (8.2%) 39/477 (8.2%) 27/905 (3%) 22/424 (5.2%)
    Blood and lymphatic system disorders
    Anaemia 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Pancytopenia 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Cardiac disorders
    Acute coronary syndrome 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Acute myocardial infarction 2/959 (0.2%) 1/477 (0.2%) 1/905 (0.1%) 0/424 (0%)
    Arrhythmia supraventricular 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Atrial tachycardia 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Cardiac arrest 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Cardiac failure congestive 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 1/424 (0.2%)
    Cardiogenic shock 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Coronary artery disease 2/959 (0.2%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Coronary artery insufficiency 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Myocardial infarction 1/959 (0.1%) 2/477 (0.4%) 0/905 (0%) 0/424 (0%)
    Myocarditis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Eye disorders
    Retinal detachment 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Gastrointestinal disorders
    Abdominal adhesions 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Abdominal pain 3/959 (0.3%) 0/477 (0%) 0/905 (0%) 2/424 (0.5%)
    Abdominal pain upper 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Colitis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Colitis ulcerative 1/959 (0.1%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Diarrhoea 1/959 (0.1%) 2/477 (0.4%) 1/905 (0.1%) 2/424 (0.5%)
    Diverticular perforation 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Enteritis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Erosive oesophagitis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Gastritis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Intestinal perforation 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Large intestine perforation 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Nausea 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Rectal haemorrhage 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 1/424 (0.2%)
    Small intestinal obstruction 1/959 (0.1%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Upper gastrointestinal haemorrhage 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Vomiting 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    General disorders
    Chest pain 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 2/424 (0.5%)
    Chills 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Fatigue 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    General physical health deterioration 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Non-cardiac chest pain 2/959 (0.2%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Pyrexia 0/959 (0%) 0/477 (0%) 0/905 (0%) 2/424 (0.5%)
    Sudden death 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Systemic inflammatory response syndrome 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Vascular stent occlusion 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Hepatobiliary disorders
    Cholecystitis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Cholecystitis acute 0/959 (0%) 1/477 (0.2%) 1/905 (0.1%) 0/424 (0%)
    Cholelithiasis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Hydrocholecystis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Immune system disorders
    Anaphylactic reaction 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Infections and infestations
    Abscess limb 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Acute hepatitis C 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Anal abscess 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Appendiceal abscess 0/959 (0%) 1/477 (0.2%) 1/905 (0.1%) 0/424 (0%)
    Appendicitis 3/959 (0.3%) 1/477 (0.2%) 1/905 (0.1%) 1/424 (0.2%)
    Bacterial colitis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Bacterial sepsis 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Bronchitis 1/959 (0.1%) 1/477 (0.2%) 1/905 (0.1%) 0/424 (0%)
    Cellulitis 0/959 (0%) 2/477 (0.4%) 2/905 (0.2%) 0/424 (0%)
    Chronic sinusitis 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Conjunctivitis bacterial 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Diverticulitis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Enteritis infectious 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Epididymitis 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Erysipelas 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Gastroenteritis 1/959 (0.1%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Gonorrhoea 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    H1n1 influenza 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Hepatitis A 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Hepatitis syphilitic 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Influenza 0/959 (0%) 2/477 (0.4%) 0/905 (0%) 0/424 (0%)
    Localised infection 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Meningitis aseptic 3/959 (0.3%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Meningitis viral 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Neurosyphilis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Osteomyelitis 1/959 (0.1%) 2/477 (0.4%) 0/905 (0%) 0/424 (0%)
    Parasitic gastroenteritis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Perineal infection 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Perirectal abscess 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Pneumonia 5/959 (0.5%) 0/477 (0%) 0/905 (0%) 2/424 (0.5%)
    Pneumonia legionella 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Pneumonia mycoplasmal 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Rectal abscess 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Reiter's syndrome 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Scrotal infection 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Secondary syphilis 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Sepsis 4/959 (0.4%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Septic shock 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Sinusitis 2/959 (0.2%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Urinary tract infection 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Viral infection 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Wound infection 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Injury, poisoning and procedural complications
    Acetabulum fracture 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Craniocerebral injury 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Head injury 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Hip fracture 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Maternal exposure during pregnancy 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Multiple fractures 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Overdose 1/959 (0.1%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Post procedural complication 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Radius fracture 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Rib fracture 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Road traffic accident 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Skin abrasion 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Skull fracture 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Wrist fracture 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis reactive 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Intervertebral disc protrusion 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Osteoarthritis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Osteonecrosis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Bone cancer metastatic 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Hodgkin's disease 1/959 (0.1%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Lung adenocarcinoma stage IV 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Non-small cell lung cancer 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Prostate cancer 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Rectal cancer 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Squamous cell carcinoma of the tongue 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Tonsil cancer 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Nervous system disorders
    Ataxia 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Cauda equina syndrome 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Cerebral haemorrhage 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Dizziness 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Embolic stroke 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Febrile convulsion 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Guillain-Barre syndrome 1/959 (0.1%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Haemorrhagic stroke 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Headache 1/959 (0.1%) 1/477 (0.2%) 0/905 (0%) 1/424 (0.2%)
    Memory impairment 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Migraine 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Seizure 2/959 (0.2%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Tension headache 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Transient ischaemic attack 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/959 (0.1%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Product Issues
    Device breakage 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Psychiatric disorders
    Acute psychosis 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Alcohol abuse 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Bipolar disorder 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Depression 0/959 (0%) 2/477 (0.4%) 0/905 (0%) 0/424 (0%)
    Drug abuse 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Hallucination 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Major depression 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Mental status changes 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Substance abuse 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Substance-induced psychotic disorder 2/959 (0.2%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Suicidal behaviour 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Suicidal ideation 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Suicide attempt 4/959 (0.4%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/959 (0.1%) 2/477 (0.4%) 1/905 (0.1%) 0/424 (0%)
    Bladder disorder 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Fanconi syndrome acquired 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Nephrolithiasis 0/959 (0%) 0/477 (0%) 0/905 (0%) 1/424 (0.2%)
    Renal colic 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Reproductive system and breast disorders
    Metrorrhagia 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Prostatitis 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 1/424 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 1/424 (0.2%)
    Chronic obstructive pulmonary disease 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Dyspnoea 2/959 (0.2%) 0/477 (0%) 1/905 (0.1%) 1/424 (0.2%)
    Non-cardiogenic pulmonary oedema 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Pleuritic pain 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Pneumothorax 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Respiratory failure 1/959 (0.1%) 0/477 (0%) 0/905 (0%) 0/424 (0%)
    Skin and subcutaneous tissue disorders
    Subcutaneous emphysema 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Social circumstances
    Substance use 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Vascular disorders
    Hypertension 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Hypertensive crisis 0/959 (0%) 0/477 (0%) 1/905 (0.1%) 0/424 (0%)
    Hypotension 0/959 (0%) 1/477 (0.2%) 0/905 (0%) 0/424 (0%)
    Other (Not Including Serious) Adverse Events
    Randomized Phase: E/C/F/TAF Randomized Phase: Stay on Baseline Treatment Regimen (SBR) Extension Phase: E/C/F/TAF From E/C/F/TAF Extension Phase: E/C/F/TAF From SBR
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 620/959 (64.7%) 286/477 (60%) 298/905 (32.9%) 144/424 (34%)
    Gastrointestinal disorders
    Diarrhoea 109/959 (11.4%) 51/477 (10.7%) 40/905 (4.4%) 22/424 (5.2%)
    Nausea 56/959 (5.8%) 18/477 (3.8%) 8/905 (0.9%) 13/424 (3.1%)
    General disorders
    Pyrexia 48/959 (5%) 21/477 (4.4%) 7/905 (0.8%) 6/424 (1.4%)
    Infections and infestations
    Bronchitis 69/959 (7.2%) 26/477 (5.5%) 17/905 (1.9%) 13/424 (3.1%)
    Nasopharyngitis 96/959 (10%) 48/477 (10.1%) 47/905 (5.2%) 20/424 (4.7%)
    Pharyngitis 56/959 (5.8%) 14/477 (2.9%) 15/905 (1.7%) 5/424 (1.2%)
    Sinusitis 58/959 (6%) 31/477 (6.5%) 25/905 (2.8%) 9/424 (2.1%)
    Syphilis 63/959 (6.6%) 38/477 (8%) 19/905 (2.1%) 9/424 (2.1%)
    Upper respiratory tract infection 168/959 (17.5%) 64/477 (13.4%) 67/905 (7.4%) 26/424 (6.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 78/959 (8.1%) 31/477 (6.5%) 19/905 (2.1%) 8/424 (1.9%)
    Back pain 70/959 (7.3%) 33/477 (6.9%) 30/905 (3.3%) 9/424 (2.1%)
    Osteopenia 67/959 (7%) 25/477 (5.2%) 28/905 (3.1%) 13/424 (3.1%)
    Nervous system disorders
    Headache 83/959 (8.7%) 25/477 (5.2%) 18/905 (2%) 9/424 (2.1%)
    Psychiatric disorders
    Depression 48/959 (5%) 30/477 (6.3%) 15/905 (1.7%) 7/424 (1.7%)
    Insomnia 58/959 (6%) 36/477 (7.5%) 12/905 (1.3%) 8/424 (1.9%)
    Respiratory, thoracic and mediastinal disorders
    Cough 73/959 (7.6%) 31/477 (6.5%) 28/905 (3.1%) 13/424 (3.1%)
    Oropharyngeal pain 57/959 (5.9%) 12/477 (2.5%) 10/905 (1.1%) 7/424 (1.7%)

    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

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01815736
    Other Study ID Numbers:
    • GS-US-292-0109
    • 2012-005114-20
    First Posted:
    Mar 21, 2013
    Last Update Posted:
    Apr 13, 2021
    Last Verified:
    Mar 1, 2021