Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Compared With a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

A Phase 3B, Randomized, Open-label Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Compared With a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

The purpose of the study was to evaluate the safety and efficacy of the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) compared with the efavirenz (EFV)/FTC/TDF STR in HIV-1 infected adults who had not previously received treatment with antiretroviral medications.

Participants were randomized in a 1:1 ratio to receive one of the study treatments. Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. A treatment duration of 96 weeks was planned, with the option for subjects in FTC/RPV/TDF STR arm to receive treatment following the Week 96 visit until FTC/RPV/TDF STR is commercially available or until Gilead Sciences elects to terminate development in that country.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: FTC/RPV/TDF; Drug: EFV/FTC/TDF

• Study Type: Interventional
• Enrollment (Actual): 799
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia, 02010
    • St Vincent's Hospital, Sydney
  • Darlinghurst, Australia, 02010
    • Taylor Square Private Clinic
  • Melbourne, Australia, 03004
    • Clinical Research - Infectious Diseases Unit Alfred Hospital
  • North Fitzroy, Australia, 03068
    • Northside Clinic
  • Prahran, Australia, 03181
    • Prahran Market Clinic
  • Surry Hills, Australia, 02010
    • Albion Street Centre
  • Sydney, Australia, 02010
    • East Sydney Doctors
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 02010
      • Holdsworth House Medical Practice
• Austria
  • Graz, Austria, A-8020
    • LKH Medical University Graz West, Department of Internal Medicine
  • Innsbruck, Austria, A6020
    • Universitätsklinikum Innsbruck Universitätsklinik für Dermatologie und Venerologie
  • Vienna, Austria, 01090
    • Department of Dermatology, Allergy, and Infectious Disease University Vienna Medical School
• Belgium
  • Antwerp, Belgium, 2000
    • Institute of Tropical Medicine
  • Brussels, Belgium, 01200
    • Cliniques universitaires Saint-Luc - UCL
  • Leuven, Belgium, 03000
    • University Hospitals Leuven
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z2C7
      • Vancouver ID Research and Care Centre Society
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Division of HIV/AIDS, St. Paul's Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital, General Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network/Toronto General Hospital
    • Toronto, Ontario, Canada, M5G 1K2
      • Maple Leaf Research Maple Leaf Medical Clinic
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • McGill University Health Center, Montreal Chest Institute
    • Montréal, Quebec, Canada, H2L 4P9
      • Clinique médicale L' Actuel
• France
  • Garches, France, 92380
    • Hôpital Raymond Poincaré
  • Lyon, France, 69288
    • Hôpital de la Croix-Rousse
  • Nantes, France, 44093
    • Chu Hotel Dieu
  • Nice, France, 06200
    • CHU Nice - Archet 1
  • Paris, France, 75018
    • Hopital Bichat Claude Bernard
  • Paris, France, 75475
    • HOSPITAL SAINT LOUIS - Services des Maladies Infectieuses
  • Paris, France, 75571
    • Hopital Saint Antoine- Service Maladies infectieuses
  • Paris, France, 75970
    • Hopital Tenon Service des Maladies infectieuses et tropicales
  • Paris cedex 13, France, 75651
    • Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses
  • Tourcoing, France, 59208
    • Centre Hospitalier de Tourcoing
• Germany
  • Berlin, Germany, 12157
    • EPIMED GmbH
  • Bonn, Germany, 53105
    • Medizinische Universitätsklinik I der Friedrich-Wilhelms Universität Bonn
  • Essen, Germany, 45122
    • Department of Dermatology University Hospital Essen
  • Frankfurt am Main, Germany, 60311
    • Private Practice Gute & Locher & Lutz, Infektiologikum
  • Freiburg, Germany, 79106
    • Division of Infectious Disease, Department of Medicine, University Hospital Freiburg
  • Hamburg, Germany, 20146
    • ICH Study Center
  • Hamburg, Germany, 20246
    • Universitätsklinikum Eppendorf Ambulanzzentrum des UKE GmbH, Infekiologie
  • München, Germany, 80335
    • MUC Research GmbH
• Italy
  • Bergamo, Italy, 24128
    • Ospedali Riuniti
  • Milan, Italy, 20127
    • IRCCS Ospedale San Raffaele Centro San Luigi, Unità Operativa di Malattie Infettive
  • Milano, Italy, 20157
    • I Div Infectious Diseases, Luigi Sacco Hospital
  • Monza, Italy, 20092
    • San Gerardo Hospital - Uo Malattie Infettive
  • Pavia, Italy, 27100
    • Foundation "IRCCS Policlinico San Matteo Hospital"
  • Rome, Italy, 00149
    • National Institute for Infectious Diseases "L. Spallanzani" IRCCS
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Onze Lieve Vrouwe Gasthuis
  • Rotterdam, Netherlands, PB 2040
    • Erasmus MC
• Portugal
  • Lisbon, Portugal, 1649-035
    • Hospital de Santa Maria - CHLN, EPE
  • Porto, Portugal, 4369-004
    • Hospital de Joaquim Urbano
  • Porto, Portugal, 4200-319
    • Serviço de Doenças Infecciosas, Hospital S. Joao
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario Alicante
  • Cataluña, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Elche, Spain, 03202
    • Hospital Universitario de Elche, Unidad de Enfermedades Infecciosas
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 Octubre
  • Madrid, Spain, 28041
    • Unidad HIV. Hospital 12 de Octubre
• Switzerland
  • Bern, Switzerland, 03010
    • Universitätsklinik für Infektiologie
  • Lausanne, Switzerland, 01011
    • CHUV
  • Zurich, Switzerland, 08091
    • University Hospital Zurich
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Edinburgh, United Kingdom, EH42XU
    • Ridu, Wgh
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital
  • London, United Kingdom, E11 BB
    • Clinical Research, Grahame Hayton Unit Ambrose King Centre, The Royal London Hospital
  • London, United Kingdom, NW32QG
    • Royal Free NHS Trust,
  • London, United Kingdom, SE7 4EH
    • Guys and St Thomas' NHS 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
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Hayward, California, United States, 94545
      • Kaiser Permanente Medical Center
    • Long Beach, California, United States, 90813
      • Living Hope Education and Research Consultants
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Medical Center
    • Los Angeles, California, United States, 90036
      • Lightsource Medical
    • Los Angeles, California, United States, 90059
      • OASIS Clinic
    • Los Angeles, California, United States, 90028
      • Jeffrey Goodman Special Care Clinic/Los Angeles Gay and Lesbian Center
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • 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, 94114
      • Metropolis Medical/Dr.Fritz
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center, San Francisco
  • Colorado
    • Denver, Colorado, United States, 80209
      • Apex Research LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Clinic
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
    • Washington, District of Columbia, United States, 20037
      • Medical Faculty Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond, M.D., P.A.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Ft. Lauderdale, Florida, United States, 33311
      • Broward General Medical 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
      • Valuhealthmd,Llc / Idocf
    • Pensacola, Florida, United States, 32504
      • Infectious Disease Associates of NW FL
    • Safety Harbor, Florida, United States, 34695
      • AHF Health Positive - Tampa Bay
    • Tampa, Florida, United States, 33614
      • St. Joseph's Hospital d/b/a Comprehensive Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
    • Atlanta, Georgia, United States, 30306
      • Emory University
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of America
    • Macon, Georgia, United States, 31201
      • Mercer University School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Clint Spencer Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins Rockland Physicians Practice and Research Group at Greenspring Station
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Community Research Initiative of New England
    • Springfield, Massachusetts, United States, 01105
      • Claudia T Martorell, MD., LLC dba 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
    • St. Louis, Missouri, United States, 63108
      • Central West Clinical Research, Inc.
    • St. Louis, Missouri, United States, 63139
      • Southampton Healthcare
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Sante Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • Albany, New York, United States, 12208
      • Upstate Infectious Disease Associates
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Flushing, New York, United States, 11355
      • New York Hospital Queens
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital--Division of Infectious Diseases
    • Mount Vernon, New York, United States, 10550
      • Greiger Clinic
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD, PC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical and Translational Research Center - UNC Hospitals
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • The Brody School of Medicine at East Carolina University
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44203
      • Summa Health System CARE Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • South Carolina
    • Columbia, South Carolina, United States, 29223
      • University of South Carolina
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75208
      • Trinity Health and Wellness Center
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Associates, Inc.
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Harlingen, Texas, United States, 78550
      • Garcia Family Health Group
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, P.A.
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Annandale, Virginia, United States, 22003
      • CARE-ID
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.
    • Spokane, Washington, United States, 99204
      • Rockwood Pulmonary and Critical Care
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Plasma HIV-1 RNA levels ≥ 2,500 copies/mL at screening
• No prior use of any approved or experimental anti-HIV drug for any length of time
• Screening genotype report showing sensitivity to EFV, FTC, TDF, and lack of the RPV mutations K101E/P, E138A/G/K/Q/R, Y181C/I/V, and H221Y
• Normal ECG
• Hepatic transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) ≤ 5 x the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 x ULN (participants with serum amylase > 5 x ULN remained eligible if serum lipase was ≤ 5 x ULN)
• Adequate renal function
• Males and Females of childbearing potential must have agreed to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study period and for 12 weeks following the last dose of study drug.
• Adult (≥ 18 years) males or non-pregnant females

Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Females who were breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Proven or suspected acute hepatitis in the 30 days prior to study entry
• Subjects receiving drug treatment for hepatitis C, or subjects who were anticipated to receive treatment for hepatitis C during the course of the study
• Subjects experiencing decompensated cirrhosis
• Had an implanted defibrillator or pacemaker
• Current alcohol or substance abuse
• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Receiving ongoing therapy or anticipated to need to initiate drugs or herbal/natural supplements during the study that are contraindicated or not recommended for use, including drugs not to be used with FTC, EFV, RPV, or TDF; or subjects with known allergies to the excipients of the FTC/RPV/TDF or EFV/FTC/TDF single-tablet regimens
• Participation in any other clinical trial without prior approval from the sponsor was prohibited while participating in this trial.
• Had been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids for immunosuppression during the study (eg, corticosteroids, immunoglobulins, and other immune-based or cytokine-based therapies)
• Had any other clinical condition or prior therapy that, in the opinion of the Investigator, would have made the participant unsuitable for the study or unable to comply with the dosing requirements

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: FTC/RPV/TDF	Drug: FTC/RPV/TDF; Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen administered orally once daily with a meal; Other Names: Complera®; Eviplera®
Experimental: EFV/FTC/TDF	Drug: EFV/FTC/TDF; Efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg single-tablet regimen administered orally once daily on an empty stomach, preferably at bedtime; Other Names: Atripla®

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 with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the US FDA snapshot algorithm. The snapshot algorithm defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the US FDA snapshot algorithm.	Baseline to Week 96
Change From Baseline in CD4 Cell Count at Week 48		Baseline to Week 48
Change From Baseline in CD4 Cell Count at Week 96		Baseline to Week 96
Change From Baseline in Fasting Total Cholesterol at Week 48		Baseline to Week 48
Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48		Baseline to Week 48
Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48		Baseline to Week 48
Change From Baseline in Fasting Triglycerides at Week 48		Baseline to Week 48
Development of HIV-1 Drug Resistance Through Week 96, All Participants	Participants who experienced either suboptimal virologic response or virologic rebound were considered to have virologic failure and were analyzed for resistance. Suboptimal virologic response was assessed at Week 8 and was defined as having HIV-1 RNA ≥ 50 copies/mL and < 1-log10 reduction from baseline at the Week 8 visit, which was confirmed at the subsequent visit. Virologic rebound was defined as having 2 consecutive visits with HIV-1 RNA ≥ 400 copies/mL after achieving HIV-1 RNA < 50 copies/mL, or as having 2 consecutive visits with > 1 log10 increase in HIV-1 RNA from their nadir. In addition, subjects who were on study drugs, had not been analyzed previously, and who had HIV-1 RNA ≥ 400 copies/mL at Week 48, Week 96, or their last visit (at or after Week 8) were also analyzed for resistance at their last visit. Subsequent to the first resistance testing, subjects experiencing repeated confirmed virologic failure were assessed for resistance retesting on a case-by-case basis.	Baseline to Week 96
Development of HIV-1 Drug Resistance Through Week 96, Participants With Viral Resistance	Resistance Analysis Set: participants with either suboptimal virologic response or virologic rebound were considered to have virologic failure and were analyzed. Suboptimal virologic response was assessed at Week 8 and was defined as having HIV-1 RNA ≥ 50 copies/mL and < 1-log10 reduction from baseline at the Week 8 visit, which was confirmed at the subsequent visit. Virologic rebound was defined as having 2 consecutive visits with HIV-1 RNA ≥ 400 copies/mL after achieving HIV-1 RNA < 50 copies/mL, or as having 2 consecutive visits with > 1 log10 increase in HIV-1 RNA from their nadir. In addition, subjects who were on study drugs, had not been analyzed previously, and who had HIV-1 RNA ≥ 400 copies/mL at Week 48, Week 96, or their last visit (at or after Week 8) were also analyzed for resistance at their last visit. Subsequent to the first resistance testing, subjects experiencing repeated confirmed virologic failure were assessed for resistance retesting on a case-by-case basis.	Baseline to Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Chair: Todd Fralich, M.D., Gilead Sciences

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: March 3, 2011
• First Submitted That Met QC Criteria: March 3, 2011
• First Posted (Estimate): March 7, 2011

Study Record Updates

• Last Update Posted (Estimate): February 25, 2015
• Last Update Submitted That Met QC Criteria: February 3, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Antiretroviral Treatment-Naïve
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Rilpivirine, Tenofovir Drug Combination
• Other Study ID Numbers: GS-US-264-0110