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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV
• Intervention / Treatment: Drug: E/C/F/TAF; Drug: E/C/F/TDF; Drug: FTC/TDF; Drug: EFV/FTC/TDF; Drug: RTV; Drug: ATV; Drug: COBI

• Study Type: Interventional
• Enrollment (Actual): 1443
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
    • Darlinghurst, New South Wales, Australia, 2010
      • East Sydney Doctors
    • Darlinghurst, New South Wales, Australia, 2010
      • Taylor Square Private Clinic
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital, Sydney
    • Surry Hills, New South Wales, Australia, 2010
      • Albion Street Centre
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Melbourne Sexual Health Clinic
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3068
      • Northside Clinic
    • South Yarra, Victoria, Australia, 3141
      • Prahran Market Clinic
• Austria
  • Graz, Austria, 8020
    • Medizinische Universität Graz
  • Vienna, Austria, 1090
    • Medizinische Universität Wien
  • Vienna, Austria, 1140
    • SMZ Baumgartner Hoehe - Otto-Wagner-Spital
• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre University Hospital
  • Ghent, Belgium, 1070
    • Hôpital Universitaire Erasme - ULB
• Brazil
  • Rio de Janeiro, Brazil, 21040-360
    • Instituto De Pesquisa Clinica Evandro Chagas - Fundação Oswaldo Cruz
  • Santo Andre, Brazil, 09060-650
    • Faculdade de Medicina do ABC
  • Sao Paulo, Brazil, 01246-900
    • São Paulo Secretaria da Saúde - Instituto De Infectologia Emilio Ribas
  • Sao Paulo, Brazil, 04121-000
    • São Paulo Secretaria da Saúde - Centro de Referência e Treinamento em DST/AIDS
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Ubc Downtown I.D. Clinic
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1K2
      • Maple Leaf Research
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network, Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 5B1
      • Clinique Medicale du Quartier Latin
    • Montreal, Quebec, Canada, H3A 1T1
      • Clinique OPUS
    • Montreal, Quebec, Canada, H2L 4P9
      • Clinique médicale l'Actuel
    • Montréal, Quebec, Canada, H2X 2P4
      • McGill University Health Centre (MUHC) - Montral Chest Institute
• Denmark
  • Copenhagen, Denmark, 2100
    • Epidemiklinikken 5112, Rigshospitalet
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Instituto Dominicano de Estudios Virologicos - IDEV
• France
  • Lyon, France, 75970
    • Hopital de la Croix Rousse
  • Nantes, France, 44093
    • CHU Hôtel Dieu
  • Nice, France, 06200
    • Archet 1 CHU de Nice - 6ème Niveau
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Paris, France, 75018
    • Bichat Hospital
  • Tourcoing, France, 59208
    • Centre Hospitalier de Tourcoing
• Germany
  • Berlin, Germany, 12157
    • EPIMED GmbH
  • Bonn, Germany, 53127
    • University of Bonn
  • Duesseldorf, Germany, 40237
    • Center for HIV and Hepatogastroenterology
  • Frankfurt am Main, Germany, 60590
    • Universitatsklinikum Frankfurt
  • Frankfurt am Main, Germany, 60311
    • Infektio Research GmbH / Infektiologikum Frankfurt
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 20146
    • ICH Study Center Hamburg
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit
  • Köln, Germany, 50937
    • University of Cologne, Department of Internal Medicine
  • München, Germany, 80335
    • MUC Research GmbH
• Italy
  • Milan, Italy, 20127
    • Fondazione Centro San Raffaele del Monte Tabor
  • Milano, Italy, 20157
    • Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
  • Rome, Italy, 00149
    • Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS
  • Torino, Italy, 10149
    • Comprensorio Amedeo Di Savoia Birago Di Vische
• Mexico
  • Guadalajara, Mexico, 44280
    • Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde"
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Onze Lieve Vrouwe Gasthuis, Afdeling Infectieziekten
  • Rotterdam, Netherlands, 3000 CA
    • Erasmus MC
• Portugal
  • Lisbon, Portugal, 1649-035
    • Hospital de Santa Maria
  • Porto, Portugal, 4202-451
    • Servico De Doencas Infecciosas - Hospital De Sao Joao
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Hope Clinical Research
  • San Juan, Puerto Rico, 00921
    • VA Caribbean Healthcare System
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
• Sweden
  • Stockholm, Sweden, 11883
    • Södersjukhuset
• Switzerland
  • Bern, Switzerland, 3010
    • Universitätsklinik für Infektiologie, Universitätsspital Bern
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
  • Zürich, Switzerland, 8091
    • University Hospital of Zürich
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital, Mahidol University
  • Bangkok, Thailand, 10330
    • HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine Chulalongkorn University
  • Bangkok, Thailand, 10700
    • Siriraj HospitalDepartment of Preventive and Social Medicine, Faculty of Medicine
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai University, Faculty of Medicine, Department of Medicine
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University
• United Kingdom
  • Brighton, United Kingdom, BN2 1ES
    • Brighton and Sussex University Hospitals NHS Trust
  • London, United Kingdom, E1 1BB
    • Barts and the London NHS Trust
  • London, United Kingdom, SW17 0QT
    • Courtyard Clinic, St. Georges Hospital
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital Foundation Trust
  • Manchester, United Kingdom, M8 5RB
    • North Manchester General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama At Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
    • Phoenix, Arizona, United States, 85006
      • Southwest Center For Hiv/Aids
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health For Life Clinic Pllc
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Costa Mesa, California, United States, 92626
      • Michael Keith Wensley, MD, Inc., A Medical Corporation
    • Long Beach, California, United States, 90813
      • Living Hope Clinical Foundation
    • Los Angeles, California, United States, 90028
      • Jeffrey Goodman Special Care Clinic
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc
    • Los Angeles, California, United States, 90036
      • Peter J Ruane, MD, Inc
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Oakland, California, United States, 94602
      • Alameda County Medical Center
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • Palo Alto, California, United States, 94303
      • Stanford University
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Group
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center, Clinical Trials Unit
    • San Francisco, California, United States, 94109
      • Metropolis Medical Group
    • San Leandro, California, United States, 94577
      • Kaiser Permanente Hospital
  • Colorado
    • Denver, Colorado, United States, 80209
      • Apex Research LLC
  • Connecticut
    • Greenwich, Connecticut, United States, 06830
      • Greenwich Hospital
    • New Haven, Connecticut, United States, 06510
      • Yale University HIV Clinical Trials Program
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
    • Washington, District of Columbia, United States, 20009
      • Whitman Walker Clinic
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physicians Group
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33311
      • Broward Health/Comprehensive Care Center
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond,M.D.,P.A.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • IDOCF/ Value Health MD, LLC
    • Tampa, Florida, United States, 33614
      • Infectious Disease Research Institute Inc.
    • Tampa, Florida, United States, 33602
      • University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department
    • Tampa, Florida, United States, 33615
      • St. Joseph's Comprehensive Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group, PC
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • University of Hawaii - Hawaii Center for AIDS
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Ruth M. Rothstein CORE Center
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Community Research Initiative of New England
    • Springfield, Massachusetts, United States, 01199
      • Baystate Infectious Diseases Clinical Research
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University
    • Saint Louis, Missouri, United States, 63108
      • Central West Clinical Research
    • Saint Louis, Missouri, United States, 63139
      • Southampton Healthcare
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care
    • Newark, New Jersey, United States, 07102
      • Saint Michaels Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • Albany, New York, United States, 12208
      • Upstate ID Association
    • Albany, New York, United States, 12209
      • Albany Medical College
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - AIDS Center
    • Flushing, New York, United States, 11355
      • New York Hospital Queens
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital, Divison of Infectious Diseases
    • Mount Vernon, New York, United States, 10550
      • Greiger Clinic
    • New York, New York, United States, 10011
      • Chelsea Village Medical, PC
    • New York, New York, United States, 10003
      • Beth Israel Medical Center- Division of Infectious Diseases
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of NC AIDS Clinical Trials Unit
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center-Myers Park
    • Durham, North Carolina, United States, 27710
      • Duke University Health System
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
  • Ohio
    • Akron, Ohio, United States, 44304
      • SUMMA Health System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health Richland
  • Texas
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Research, Inc.
    • Dallas, Texas, United States, 75215
      • AIDS Arms, Inc./ Peabody Health Center
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Harlingen, Texas, United States, 78550
      • Garcia's Family Health Group
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, P.A.
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Clinical Alliance for Research & Education, Infectious Diseases (CARE-ID)
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: FTC/TDF; 200/300 mg tablet administered orally once daily; Other Names: Truvada®; 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: COBI; 150 mg tablet administered orally once daily; Other Names: Tybost®; GS-9350

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Creatinine at Week 48		Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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.	Week 96
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at 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.	Baseline; Week 48
Percent Change From Baseline in Spine BMD at Week 48	Spine BMD was assessed by DXA scan. BMD is calculated as g/cm^2; the mean (SD) percentage change is presented.	Baseline; Week 48
Change From Baseline in the Overall EFV-related Symptom Assessment Score at 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.	Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at 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.	Week 48
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at 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.	Week 96
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at 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.	Baseline; Week 48
Change From Baseline in CD4 Cell Count at Weeks 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.	Baseline; Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Orkin C, DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Vandercam B, de Wet J, Rockstroh J, Lazzarin A, Rijnders B, Podzamczer D, Thalme A, Stoeckle M, Porter D, Liu HC, Cheng A, Quirk E, SenGupta D, Cao H. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV. 2017 May;4(5):e195-e204. doi: 10.1016/S2352-3018(17)30031-0. Epub 2017 Mar 2.
• Gupta SK, Post FA, Arribas JR, Eron JJ Jr, Wohl DA, Clarke AE, Sax PE, Stellbrink HJ, Esser S, Pozniak AL, Podzamczer D, Waters L, Orkin C, Rockstroh JK, Mudrikova T, Negredo E, Elion RA, Guo S, Zhong L, Carter C, Martin H, Brainard D, SenGupta D, Das M. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS. 2019 Jul 15;33(9):1455-1465. doi: 10.1097/QAD.0000000000002223.
• Mills A, Arribas JR, Andrade-Villanueva J, DiPerri G, Van Lunzen J, Koenig E, Elion R, Cavassini M, Madruga JV, Brunetta J, Shamblaw D, DeJesus E, Orkin C, Wohl DA, Brar I, Stephens JL, Girard PM, Huhn G, Plummer A, Liu YP, Cheng AK, McCallister S; GS-US-292-0109 team. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis. 2016 Jan;16(1):43-52. doi: 10.1016/S1473-3099(15)00348-5. Epub 2015 Nov 2.
• Brown T, Yin MT, Gupta S, Katlama C, et al. Switching from TDF to TAF in HIV-infected adults with low BMD: a pooled analysis. 24th Annual Conference on Retroviruses and Opportunistic Infections (CROI) - CROI Foundation 2017; poster presentation: abstract #683.
• Podzamczer D, Viciana P, Rijnders B, Shalit P, et al. Switching from Tenofovir disoproxil fumarate to tenofovir alafenamide in patients with high risk for chronic kidney disease. 8th National Congress of the AIDS Study Group (GESIDA) and Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) held jointly with the 9th Teacher Meeting of AIDS Research Network 2016; poster presentation: abstract #P-188.
• Orkin C, Rjinders B, Stephan C, McKellar M, et al. Switching from boosted atazanavir (ATV) plus FTC/TDF to a TAF-based single tablet regimen (STR): Week 48 data in virologically suppressed adults. Annual Conference of the British Association for Sexual Health and HIV (BASHH) 2016; poster presentation: abstract # P045.
• Mills A, Andrade J, Koenig E, et al. Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: data in virologically suppressed adults through 48 weeks of treatment. 13th Congress for Infectious Diseases and Tropical Medicine (KIT) 2016; poster presentation: abstract #eP-038.
• Overton ET, Shalit P, Crofoot G, Benson P, et al. Switch from TDF regimens to E/C/F/TAF is associated with improved bone mineral density (BMD), decreased serum PTH and decreased bone turnover biomarkers. 56th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held Jointly with the 2016 Annual Meeting on Microbe - American Society for Microbiology (ASM) 2016; poster presentation: abstract #PW-027.
• Huhn G, Rijnders B, Thompson M, Tebas P, et al. Switching from TDF to TAF in patients with high risk for CKD. 56th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held Jointly with the 2016 Annual Meeting on Microbe - American Society for Microbiology (ASM) 2016; oral presentation: https://www.natap.org/2016/HIV/062116_01.htm.
• Abram M, Margot NA, Cox S, Ram RR, et al. Pooled week-48 analysis of HIV-1 drug resistance in E/C/F/TAF (Genvoya) phase 3 studies. 23rd Annual Conference on Retroviruses and Opportunistic Infections (CROI) - CROI Foundation 2016, poster presentation: abstract #496.
• Abram M, Margot NA, Cox S, Ram RR, et al. Pooled week-48 analysis of HIV-1 drug resistance in E/C/F/TAF (Genvoya) phase 3 studies. 25th International HIV Drug Resistance Workshop - Informed Horizons, LLC 2016; poster presentation: abstract #33.
• Mills A, Andrade J, Di Perri G, Van Lunzen J, et al. Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: data in virologically suppressed adults through 48 weeks of treatment. 8th Biennial Conference on HIV Pathogenesis and Treatment and Prevention of the International AIDS Society (IAS) 2015; oral presentation: abstract #TUAB0102.
• Shamblaw D, Van Lunzen J, Orkin C, Bloch M, eta al. Switching from Atripla (ATR) to a tenofovir alafenamide (TAF)-based single tablet regimen: week 48 data in virologically suppressed adults. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2015; oral presentation; https://natap.org/2015/ICAAC/ICAAC_13.htm.
• Thompson M, Morales-Ramirez J, Mcdonald C, Rachlis A, et al. Switching from a tenofovir disoproxil fumarate (TDF) to a tenofovir alafenamide (TAF)-based single tablet regimen (STR): Week 48 data in HIV-1 infected virologically suppressed adults. Spring Conference of the Society for Healthcare Epidemiology of America (SHEA) 2015; oral presentation: abstract #725.
• Rijnders B, Stephan C, Lazzarin A, Squires K, et al. Switching from ritonavir or cobicistat boosted atazanavir (ATV) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) to a tenofovir alafenamide (TAF)-based single tablet regimen (STR): week 48 data in virologically suppressed adults. 15th European AIDS Conference (EACS) and 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV 2015; poster presentation: abstract #577.
• Lutz T, Benson P, Goffard J-C, Haubrich R, et al. Patient reported outcomes (PRO) over 48 weeks in a randomized, open-label trial of patients with HIV switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF). 15th European AIDS Conference (EACS) and 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV 2015; poster presentation: abstract #324.
• Viciana P, Mills A, Andrade J, Diperri G, et al. Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: data in virologically suppressed adults through 48 weeks of treatment. 7th National Congress of the AIDS Study Group (GESIDA) and Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) held jointly with the 8th Teacher Meeting of AIDS Research Network 2015; oral presentation: abstract #PO-08.
• Mills A, Andrade-Villanueva J, DiPerri G, Van Luzen J, et al. Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: Data in virologically suppressed adults through 48 weeks of treatment. 8th Annual International AIDS Society meeting 2015; oral presentation: abstract #839.
• Thompson M, Brar I, Brinson C, Creticos C, et al. Tenofovir alafenamide vs tenofovir DF in women: pooled analysis of 7 clinical trials. Annual Meeting of the American Pharmacists Association (APhA) - Virtual 2020; poster presentation: abstract #209.
• Stellbrink H, Gandhi-Patel B, Zhong L, Das M, et al. Safety and efficacy of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people with HIV aged 50 years and older. Annual Meeting of the American Pharmacists Association (APhA) - Virtual 2020; poster presentation: abstract #205.
• Stellbrink H-J, Post FA, Podzamczer D, Arribas J, et al. Safety and efficacy of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people with HIV aged 50 years and older. 15th Congress on Infectious Diseases and Tropical Medicine - German Society for Infectious Diseases (DPID) held jointly with the 29th Annual Meeting of the German Society for Pediatric Infectiology (DGPI) 2020; poster presentation: abstract #A-343.
• Hermansson L, Yilmaz A, Price RW, Nilsson S, McCallister S, Makadzange T, Das M, Zetterberg H, Blennow K, Gisslen M. Plasma concentration of neurofilament light chain protein decreases after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate. PLoS One. 2019 Dec 11;14(12):e0226276. doi: 10.1371/journal.pone.0226276. eCollection 2019.
• Stellbrink H-J, Post FA, Podzamczer D, Arribas J, et al. Safety and efficacy of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people with HIV aged 50 years and older. 17th European AIDS Conference of the European AIDS Clinical Society (EACS) 2019; poster presentation: abstract #PE9-50.
• Pepperrell T, Hughes S, Gotham D, Pozniak A, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate - is there a true difference in safety? 17th European AIDS Conference of the European AIDS Clinical Society (EACS) 2019; poster presentation: abstract #PE3-8.
• Thompson M, Brar I, Brinson C, Creticos C, et al. Tenofovir alafenamide vs. tenofovir DF in women: pooled analysis of 7 clinical trials. 9th Edition International Workshop on HIV and Women - Virology Education 2019; poster presentation: abstract #21.
• Dejesus E, Federico Andrade Villanueva J, Ramon Arribas Lopez J, Brinson C, et al. Tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in hispanic/latinx and black participants: efficacy, bone and renal safety results from a pooled analysis of 7 clinical trials. IDWeek Meeting of the Infectious Diseases Society of America (IDSA) 2019; poster presentation: abstract #318.
• Walmsley S, Andany N, Brar I, Brinson C, et al. Tenofovir alafenamide VS tenofovir DF in women: pooled analysis of 7 clinical trials. 28th Annual Canadian Conference on HIV/AIDS Research - Canadian Association for HIV Research (CAHR) 2019; poster presentation: abstract #CSP9.04.
• Kim YS, Oka S, Chetchotisakd P, Clarke A, Supparatpinyo K, Avihingsanon A, Ratanasuwan W, Kiertiburanakul S, Ruxrungtham K, Yang S, Guo S, Liu Y, Das M, Tran D, McColl D, Corales R, Nguyen C, Piontkowsky D. Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials. HIV Res Clin Pract. 2019 Jul 8:1-9. doi: 10.1080/15284336.2019.1589232. Online ahead of print.
• Hermansson L, Price RW, Yilmaz A, Nilsson S, et al. Effect on plasma NFL, a marker or neuronal injury, after switching from TDF to TAF. Annual Conference on Retroviruses and Opportunistic Infections (CROI) - CROI Foundation 2019; oral presentation: abstract #127.
• Thompson M, Brar I, Brinson C, Creticos C, et al. Tenofovir alafenamide VS tenofovir DF in women: pooled analysis of 7 clinical trials. Annual Conference on Retroviruses and Opportunistic Infections (CROI) - CROI Foundation 2019; poster presentation: abstract #519.
• Orkin C, Castelli F, Yazdanpanah Y, Rockstroh J, et al. Cardiovascular disease risk assessments and fasting lipid changes in virologically suppressed patients randomized to switch to tenofovir alafenamide versus continuing tenofovir disoproxil fumarate. 22nd International AIDS Conference - International AIDS Society 2018; poster presentation: abstract #TUPEB104.
• Brown TT, Yin MT, Gupta SK, Short WR, et al. Combined effects of bisphosphonates & TDF->TAF switch in HIV+ adults with low BMD. Annual Conference on Retroviruses and Opportunistic Infections (CROI) - CROI Foundation 2018; poster presentation: abstract #724.
• DeJesus E, Haas B, Segal-Maurer S, Ramgopal MN, Mills A, Margot N, Liu YP, Makadzange T, McCallister S. Superior Efficacy and Improved Renal and Bone Safety After Switching from a Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through 96 Weeks of Treatment. AIDS Res Hum Retroviruses. 2018 Apr;34(4):337-342. doi: 10.1089/AID.2017.0203. Epub 2018 Mar 20.
• Goldstein D, Ward D, Brinson C, Crofoot G, et al. Week 96 efficacy and safety of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in older, HIV-Infected virologically-suppressed adults. Annual Meeting of the American Geriatrics Society (AGS) 2017; poster presentation: abstract #A90.
• Ward D, Thompson M, Goldstein D, Brinson C, et al. Week 96 efficacy and safety of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in older, HIV-infected treatment-naïve adults. Annual Meeting of the American Geriatrics Society (AGS) 2017; poster presentation: abstract #A91.
• Choe S, Podzamvzer D, Tashima K, McNicholl I, and McCallister S. Utilizing phase 3 clinical trial data to assess adverse event (AE) frequency of a potentially interacting medication (PIM) amlodipine with elvitegravir/cobicistat (EVG/COBI). Midyear Clinical Meeting of the American Society of Health-System Pharmacists (ASHP) 2017; poster presentation: abstract #7-068.
• Yin M, Gupta S, Nguyen-Cleary T, Mora M, and Das M. Switching from TDF to TAF in HIV-infected adults with low BMD: A pooled analysis. Congress on HIV and Hepatitis in the Americas - ViiV Healthcare UK Limited 2017; poster presentation: abstract #P021.
• Podzamczer D, Tashima K, Daar E, McGowan J, et al. Utilizing phase 3 clinical trial data to assess adverse event (AE) frequency of a potentially interacting medication (PIM) amlodipine with elvitegravir/cobicistat (EVG/COBI). International Congress of Drug Therapy in HIV Infection - International AIDS Society 2016; poster presentation: abstract #P314.
• Dejesus E, Haas B, Segal-Maurer S, Ramgopal M, et al. Superior efficacy and improved renal and bone safety after switching from a tenofovir disoproxil fumarate (TDF) regimen to a tenofovir alafenamide (TAF) based regimen through 96 weeks (W96) of treatment. 56th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held Jointly with the 2016 Annual Meeting on Microbe - American Society for Microbiology (ASM) 2016; poster presentation: abstract # LB-087.
• Viciana P, Rijnders B, Shalit P, Liu Y et al. Cambio desde TDF a TAF en pacientes en alto riesgo de erc. 18th Congress of the Andalusian Society of Infectious Diseases (SAID) 2016; poster presentation: abstract #P-070.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2013
• Primary Completion (Actual): March 16, 2015
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 19, 2013
• First Posted (Estimate): March 21, 2013

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: HIV; HIV 1 Infected; Virologically-Suppressed
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-US-292-0109; 2012-005114-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No