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
- Conditions
- HIV-1 Infection
- Interventions
- Drug: FTC/RPV/TDFDrug: EFV/FTC/TDF
- Registration Number
- NCT01309243
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 799
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FTC/RPV/TDF FTC/RPV/TDF - EFV/FTC/TDF EFV/FTC/TDF -
- Primary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48 Baseline to Week 48 Development of HIV-1 Drug Resistance Through Week 96, Participants With Viral Resistance Baseline to Week 96 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.
Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48 Baseline to Week 48 Development of HIV-1 Drug Resistance Through Week 96, All Participants Baseline to Week 96 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.
Change From Baseline in Fasting Triglycerides at Week 48 Baseline to Week 48 Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Baseline to Week 96 The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the US FDA snapshot algorithm.
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
Trial Locations
- Locations (150)
Universitätsklinikum Innsbruck Universitätsklinik für Dermatologie und Venerologie
🇦🇹Innsbruck, Austria
University of California, Davis
🇺🇸Sacramento, California, United States
Johns Hopkins Rockland Physicians Practice and Research Group at Greenspring Station
🇺🇸Lutherville, Maryland, United States
Capital Medical Associates, PC
🇺🇸Washington, District of Columbia, United States
Whitman-Walker Clinic
🇺🇸Washington, District of Columbia, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
South Jersey Infectious Disease
🇺🇸Somers Point, New Jersey, United States
Cliniques Universitaires Saint-Luc - UCL
🇧🇪Brussels, Belgium
University Hospitals Leuven
🇧🇪Leuven, Belgium
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Clinique médicale L' Actuel
🇨🇦Montréal, Quebec, Canada
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
Jeffrey Goodman Special Care Clinic/Los Angeles Gay and Lesbian Center
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Oasis Clinic
🇺🇸Los Angeles, California, United States
Anthony Mills MD Inc
🇺🇸Los Angeles, California, United States
Orange Coast Medical Group
🇺🇸Newport Beach, California, United States
North Shore University Hospital--Division of Infectious Diseases
🇺🇸Manhasset, New York, United States
University of South Carolina
🇺🇸Columbia, South Carolina, United States
AHF Research Center
🇺🇸Beverly Hills, California, United States
Kaiser Permanente Medical Center
🇺🇸Los Angeles, California, United States
Clinical and Translational Research Center - UNC Hospitals
🇺🇸Chapel Hill, North Carolina, United States
Southwest Care Center
🇺🇸Sante Fe, New Mexico, United States
AHF Health Positive - Tampa Bay
🇺🇸Safety Harbor, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
St Vincent's Hospital, Sydney
🇦🇺Darlinghurst, Australia
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Gordon E. Crofoot MD PA
🇺🇸Houston, Texas, United States
Ricky K. Hsu, Md, Pc
🇺🇸New York, New York, United States
Taylor Square Private Clinic
🇦🇺Darlinghurst, Australia
Clinical Research - Infectious Diseases Unit Alfred Hospital
🇦🇺Melbourne, Australia
Emory University
🇺🇸Atlanta, Georgia, United States
Infectious Disease Specialists of America
🇺🇸Decatur, Georgia, United States
Howard Brown Health Center
🇺🇸Chicago, Illinois, United States
Southampton Healthcare
🇺🇸St. Louis, Missouri, United States
Peter Shalit, M.D.
🇺🇸Seattle, Washington, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Broward General Medical Center
🇺🇸Ft. Lauderdale, Florida, United States
Claudia T Martorell, MD., LLC dba The Research Institute
🇺🇸Springfield, Massachusetts, United States
Gary J. Richmond, M.D., P.A.
🇺🇸Fort Lauderdale, Florida, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
Mercer University School of Medicine
🇺🇸Macon, Georgia, United States
Greiger Clinic
🇺🇸Mount Vernon, New York, United States
Northside Clinic
🇦🇺North Fitzroy, Australia
Central West Clinical Research, Inc.
🇺🇸St. Louis, Missouri, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
Upstate Infectious Disease Associates
🇺🇸Albany, New York, United States
Summa Health System Care Center
🇺🇸Akron, Ohio, United States
Garcia Family Health Group
🇺🇸Harlingen, Texas, United States
CARE-ID
🇺🇸Annandale, Virginia, United States
Prahran Market Clinic
🇦🇺Prahran, Australia
CHUV
🇨🇭Lausanne, Switzerland
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Atlanta ID Group
🇺🇸Atlanta, Georgia, United States
Valuhealthmd,Llc / Idocf
🇺🇸Orlando, Florida, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Wohlfeiler, Piperato and Associates, LLC
🇺🇸Miami Beach, Florida, United States
Infectious Disease Associates of NW FL
🇺🇸Pensacola, Florida, United States
Rosedale Infectious Diseases
🇺🇸Huntersville, North Carolina, United States
Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
New York Hospital Queens
🇺🇸Flushing, New York, United States
Southwest Infectious Disease Associates, Inc.
🇺🇸Dallas, Texas, United States
Maple Leaf Research Maple Leaf Medical Clinic
🇨🇦Toronto, Ontario, Canada
Department of Dermatology, Allergy, and Infectious Disease University Vienna Medical School
🇦🇹Vienna, Austria
University Hospital Zurich
🇨🇭Zurich, Switzerland
Rockwood Pulmonary and Critical Care
🇺🇸Spokane, Washington, United States
Holdsworth House Medical Practice
🇦🇺Darlinghurst, New South Wales, Australia
Hopital Bichat Claude Bernard
🇫🇷Paris, France
ICH Study Center
🇩🇪Hamburg, Germany
Ridu, Wgh
🇬🇧Edinburgh, United Kingdom
Hôpital de la Croix-Rousse
🇫🇷Lyon, France
Unidad HIV. Hospital 12 de Octubre
🇪🇸Madrid, Spain
Guys and St Thomas' NHS trust
🇬🇧London, United Kingdom
Hospital Universitari de Bellvitge
🇪🇸Cataluña, Spain
Royal Free NHS Trust,
🇬🇧London, United Kingdom
LKH Medical University Graz West, Department of Internal Medicine
🇦🇹Graz, Austria
Institute of Tropical Medicine
🇧🇪Antwerp, Belgium
Hospital de Santa Maria - CHLN, EPE
🇵🇹Lisbon, Portugal
Hospital de Joaquim urbano
🇵🇹Porto, Portugal
Centre Hospitalier de Tourcoing
🇫🇷Tourcoing, France
Albion Street Centre
🇦🇺Surry Hills, Australia
East Sydney Doctors
🇦🇺Sydney, Australia
Hospital Universitario de Elche, Unidad de Enfermedades Infecciosas
🇪🇸Elche, Spain
Division of HIV/AIDS, St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
HOSPITAL SAINT LOUIS - Services des Maladies Infectieuses
🇫🇷Paris, France
Clinical Research Puerto Rico
🇵🇷San Juan, Puerto Rico
IRCCS Ospedale San Raffaele Centro San Luigi, Unità Operativa di Malattie Infettive
🇮🇹Milan, Italy
Hopital Raymond Poincare
🇫🇷Garches, France
CHU Nice - Archet 1
🇫🇷Nice, France
North Manchester General Hospital
🇬🇧Manchester, United Kingdom
Royal Sussex County Hospital
🇬🇧Brighton, United Kingdom
Hopital Saint Antoine- Service Maladies infectieuses
🇫🇷Paris, France
Hospital La Paz
🇪🇸Madrid, Spain
EPIMED GmbH
🇩🇪Berlin, Germany
Department of Dermatology University Hospital Essen
🇩🇪Essen, Germany
Medizinische Universitätsklinik I der Friedrich-Wilhelms Universität Bonn
🇩🇪Bonn, Germany
Clinical Research, Grahame Hayton Unit Ambrose King Centre, The Royal London Hospital
🇬🇧London, United Kingdom
The Ottawa Hospital, General Campus
🇨🇦Ottawa, Ontario, Canada
McGill University Health Center, Montreal Chest Institute
🇨🇦Montreal, Quebec, Canada
Erasmus MC
🇳🇱Rotterdam, Netherlands
Hospital Universitario 12 Octubre
🇪🇸Madrid, Spain
Chu Hotel Dieu
🇫🇷Nantes, France
Vancouver ID Research and Care Centre Society
🇨🇦Vancouver, British Columbia, Canada
Hospital General Universitario Alicante
🇪🇸Alicante, Spain
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Serviço de Doenças Infecciosas, Hospital S. Joao
🇵🇹Porto, Portugal
University Health Network/Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Universitätsklinik für Infektiologie
🇨🇭Bern, Switzerland
Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses
🇫🇷Paris cedex 13, France
Private Practice Gute & Locher & Lutz, Infektiologikum
🇩🇪Frankfurt am Main, Germany
MUC Research GmbH
🇩🇪München, Germany
Universitätsklinikum Eppendorf Ambulanzzentrum des UKE GmbH, Infekiologie
🇩🇪Hamburg, Germany
Division of Infectious Disease, Department of Medicine, University Hospital Freiburg
🇩🇪Freiburg, Germany
The Kinder Medical Group
🇺🇸Miami, Florida, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Clint Spencer Clinic
🇺🇸Honolulu, Hawaii, United States
Foundation "IRCCS Policlinico San Matteo Hospital"
🇮🇹Pavia, Italy
Ospedali Riuniti
🇮🇹Bergamo, Italy
I Div Infectious Diseases, Luigi Sacco Hospital
🇮🇹Milano, Italy
San Gerardo Hospital - Uo Malattie Infettive
🇮🇹Monza, Italy
National Institute for Infectious Diseases "L. Spallanzani" IRCCS
🇮🇹Rome, Italy
Hopital Tenon Service des Maladies infectieuses et tropicales
🇫🇷Paris, France
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
Apex Research LLC
🇺🇸Denver, Colorado, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
St. Joseph's Hospital d/b/a Comprehensive Research Institute
🇺🇸Tampa, Florida, United States
Northstar Medical Center
🇺🇸Chicago, Illinois, United States
Trinity Health and Wellness Center
🇺🇸Dallas, Texas, United States
Therapeutic Concepts, P.A.
🇺🇸Houston, Texas, United States
Tarrant County Infectious Disease Associates
🇺🇸Fort Worth, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Living Hope Education and Research Consultants
🇺🇸Long Beach, California, United States
Lightsource Medical
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
East Bay AIDS Center
🇺🇸Oakland, California, United States
La Playa Medical Group and Clinical Research
🇺🇸San Diego, California, United States
Metropolis Medical/Dr.Fritz
🇺🇸San Francisco, California, United States
Kaiser Permanente Medical Center, San Francisco
🇺🇸San Francisco, California, United States
Dupont Circle Physician's Group
🇺🇸Washington, District of Columbia, United States
Community Research Initiative of New England
🇺🇸Boston, Massachusetts, United States
Kaiser Permanente Medical Group
🇺🇸Sacramento, California, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Philadelphia FIGHT
🇺🇸Philadelphia, Pennsylvania, United States
The Brody School of Medicine at East Carolina University
🇺🇸Greenville, North Carolina, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
Chelsea and Westminster Hospital
🇬🇧London, United Kingdom
Montefiore Medical Center
🇺🇸Bronx, New York, United States