Safety and Efficacy Study of Switching From Epzicom to Truvada (SWIFT)

A Prospective, Randomized, Open Label Phase IV Study to Evaluate the Rationale of Switching From Fixed Dose Abacavir (ABC)/Lamivudine (3TC) to Fixed Dose Tenofovir DF (TDF)/Emtricitabine (FTC) in Virologically Suppressed, HIV-1 Infected Patients Maintained on a Ritonavir Boosted Protease Inhibitor Containing Antiretroviral Regimen

This protocol describes a prospective, randomized, open-label, multicenter study to evaluate the safety and efficacy of switching from fixed dose abacavir (ABC)/lamivudine (3TC) to fixed dose emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in virologically suppressed, human immunodeficiency virus type 1 (HIV-1) infected subjects maintained on a ritonavir-boosted protease inhibitor (PI/r)-containing antiretroviral (ARV) regimen. Duration of treatment is 48 weeks.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); Drug: abacavir (ABC)/lamivudine (3TC)

Detailed Description

This protocol describes a prospective, randomized, open-label, multicenter study to evaluate the safety and efficacy of switching from fixed dose ABC/3TC to fixed dose FTC/TDF in virologically suppressed, HIV-1 infected subjects maintained on a PI/r-containing ARV regimen.

Subjects were stratified based on the PI/r (ie, lopinavir/ritonavir [LPV/r] versus other boosted PIs) in their regimen, and the presence versus absence of comorbidities at screening (diabetes mellitus or cardiovascular disease such as hypertension, coronary artery disease, hyperlipidemia, history of myocardial infarction, cardiomyopathy, valvular heart disease, congenital heart disease, stroke, peripheral vascular disease, or arrhythmias). Subjects were randomized 1:1 to switch to FTC/TDF+PI/r or to continue on their existing regimen.

Subjects received study treatment for 48 weeks.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • University of British Columbia
  • Ontario
    • Toronto, Ontario, Canada, M4T 3A7
      • CascAids Research
    • Toronto, Ontario, Canada, M4J 1V8
      • Canadian Immunodeficiency Research Collaborative Incorporated
  • Quebec
    • Montreal, Quebec, Canada, H2L5B1
      • Clinique Du Quartier Latin
• Puerto Rico
  • Ponce, Puerto Rico, 00732
    • Instituto De Investigacion Cientifica Del Sur
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico Inc
  • San Juan, Puerto Rico, 00936
    • University of Puerto Rico
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health for Life Clinic, PLLC
  • California
    • Beverly Hills, California, United States, 90210
      • Vista Medical Partners
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group
    • Beverly Hills, California, United States, 90211
      • AHF
    • Fountain Valley, California, United States, 92708
      • Center for Special Immunology
    • 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, 90036
      • Peter J. Ruane, MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony M Mills, MD
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Northridge, California, United States, 91324
      • Tarzana Treatment Center
    • Oakland, California, United States, 94602
      • Alameda County Medical Center
    • San Francisco, California, United States, 94115
      • Metropolis Medical
    • San Francisco, California, United States, 94114
      • Health Management Institute, Inc.
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
      • Blick Medical Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond, MD, PA, Inc.
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Centers
    • Fort Lauderdale, Florida, United States, 33308
      • Life Way Inc.
    • Ft. Lauderdale, Florida, United States, 33306
      • Biogenomx Research Institute, LLC
    • Ft. Lauderdale, Florida, United States, 33311
      • HIV Clinical Research
    • Jacksonville, Florida, United States, 32206
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Miami, Florida, United States, 33176
      • South Florida Infectious Diseases and Tropical Medicine Center
    • Miami, Florida, United States, 33190
      • Community Health of South Florida Inc.
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Pensacola, Florida, United States, 32504
      • Infectious Diseases Associates of NW FL
    • Port St. Lucie, Florida, United States, 34952
      • Associates in Infectious Diseases
    • Safety Harbor, Florida, United States, 34695
      • Barry M. Rodwick, M.D.
    • Tampa, Florida, United States, 33617
      • Clinical Pharmacology Services
    • Tampa, Florida, United States, 33614
      • Infectious Disease Research Institute, Inc.
    • Tampa, Florida, United States, 33602
      • USF Health
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Infectious Disease Solutions
    • Atlanta, Georgia, United States, 30309
      • Atlanta Infectious Disease Group, PC
    • Atlanta, Georgia, United States, 30318
      • Family Healthcare of Atlanta PC
    • Savannah, Georgia, United States, 31401
      • Chatham County Health Department
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Chase Brexton Health Services
  • Massachusetts
    • Framingham, Massachusetts, United States, 01702
      • MetroWest Medical Center
    • Springfield, Massachusetts, United States, 01107
      • The Research Institute
    • Springfield, Massachusetts, United States, 01107
      • Community Research Initiative of New England - West
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • East Lansing, Michigan, United States, 48824
      • Michigan State University, College of Osteopathic Medicine
    • Grosse Point Woods, Michigan, United States, 48236
      • St. John Hospital Internal Medicine Clinic - Mack Office Building
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Abbott Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55145
      • Hennepin County Medical Center
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Associates, PA
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New York
    • Albany, New York, United States, 23309
      • Upstate Infectious Diseases Associates
    • Mount Vernon, New York, United States, 10550
      • Greiger Clinic
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD, PC
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Rochester, New York, United States, 14604
      • AIDS Community Health Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • ID Consultants, P.A.
    • Greenville, North Carolina, United States, 27858
      • East Carolina University The Brody School of Medicine
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Akron, Ohio, United States, 44394
      • Summa Health System CARE Center
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center at Dallas
    • Dallas, Texas, United States, 75204
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75246
      • North Texas Inf. Disease Consultants
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Harlingen, Texas, United States, 78550
      • Valley AIDS Counsel
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot, MD, PA
  • Washington
    • Spokane, Washington, United States, 99204
      • Daniel Coulston, MD
  • 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

Inclusion Criteria:

• Adult (greater than or equal to 18 years) males or non-pregnant, non-lactating females
• HIV-1 infected subjects currently receiving a ritonavir-boosted protease inhibitor and fixed-dose ABC/3TC regimen continuously for greater than or equal to 3 months

• HIV infection as documented by a validated HIV antibody enzyme-linked immunosorbent assay (ELISA) and confirmed by one of the following:

  • Immunoblot detection of HIV antibody
  • Positive HIV-1 blood culture
  • Positive HIV-1 serum P24 antigen
  • HIV-1 plasma viremia greater than 1000 copies/mL by polymerase chain reaction (PCR) or branched-chain deoxyribonucleic acid (bDNA) method
  • Detection of proviral DNA by PCR

(If confirmation of HIV infection is not available then repeat testing of HIV antibody will be required)

• Two consecutive plasma HIV-1 RNA concentration less than 200 copies/mL. The two HIV-1 RNA determinations ensure that the subject has been virologically-suppressed for at least 3 months prior to study entry:

  • The subject must have a plasma HIV-1 RNA level less than 200 copies/mL using the AmpliPrep/Taqman HIV-1 Test or Roche Amplicor HIV-1 Monitor Test Version 1.5 Ultrasensitive method at least 3 months prior to the screening visit, as the "qualifying HIV-1 RNA."
  • HIV-1 RNA less than 200 copies/mL measured by bDNA (Chiron 3.0) may be used as a qualifying HIV-1 RNA for entry to the study but not for the confirmatory HIV-1 RNA.
  • The subject must have a confirmed second plasma HIV-1 RNA less than 200 copies/mL at screening, as the "confirmatory HIV-1 RNA."
  • The subject must not have a plasma HIV-1 RNA greater than or equal to 200 copies/mL between the qualifying and confirmatory HIV-1 RNA measurements.
• Subjects receiving lipid-lowering agents (LLA) will be allowed; however, LLAs must be stable for greater than or equal to 3 months prior to study entry.
• Adequate renal function defined as a calculated CLcr greater than or equal to 50 mL/min according to the Cockcroft-Gault formula
• Negative serum pregnancy test (females of childbearing potential only)
• Hepatic transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 5 X upper limit of normal
• Males and females (of childbearing potential, ie, a non-menopausal female or a female with menopause < 2 years, and who has not had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure; this definition includes a young woman who has not yet started menstruating), and must agree to avoid pregnancy by sexual abstinence, or utilization of a highly effective method of birth control throughout the study period and for 30 days following discontinuation of study drug
• The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures

Exclusion Criteria:

• Subjects receiving ABC/3TC and a PI without ritonavir
• Subjects receiving other ARV agents (eg, 2 protease inhibitors boosted with low-dose ritonavir (ie, "double-boosted PI regimens"), nonnucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors, TDF, or other nucleoside reverse transcriptase inhibitor [NRTIs]) in addition to ABC/3TC and a ritonavir-boosted protease inhibitor
• Have known resistance to any of the study agents at any time in the past including NRTI resistance mutations (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations) and/or PI resistance mutations
• A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed (with the exception of CD4 criteria) within 30 days of baseline
• Previous therapy with agents with systemic myelosuppressive, pancreatoxic, hepatotoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment
• Proven or suspected acute hepatitis in the 30 days prior to study entry
• Anticipated need to initiate drugs during the study that are contraindicated with protease inhibitors (except upon approval by Gilead)

• Receiving ongoing therapy with any of the following (administration of any of the following medications must be discontinued at least 30 days prior to the Baseline visit and for the duration of the study period):

  • Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir, cisplatin, foscarnet, intravenous pentamidine, other agents with significant nephrotoxic potential)
  • Adefovir dipivoxil
  • Probenecid
  • Systemic chemotherapeutic agents (ie, cancer treatment medications)
  • Systemic corticosteroids
  • Interleukin-2 (IL-2)
  • Investigational agents (except upon approval by Gilead)
• Pregnant or lactating subjects
• Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication
• Current alcohol or substance abuse judged by the investigator to potentially interfere with subject adherence
• Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of baseline and are not anticipated to require systemic therapy during the study.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antimicrobial therapy within 15 days prior to screening
• Prior history of significant renal or bone disease
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements
• Known hypersensitivity to the study drugs, the metabolites or formulation excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FTC/TDF (Truvada [TVD]) + PI/r; Participants in this group received fixed-dose combination FTC 200 mg/TDF 300 mg (Truvada [TVD]) for 48 weeks. The prestudy ritonavir-boosted PI was continued unmodified through the 48 weeks of the study.	Drug: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC 200 mg/TDF 300 mg tablet, once a day; Other Names: Truvada
ACTIVE_COMPARATOR: ABC/3TC + PI/r; Participants in this group continued their prestudy therapy - ABC 600 mg/3TC 300 mg administered as one tablet orally once daily (Epzicom) plus ritonavir-boosted PI regimen, given orally for 48 weeks.	Drug: abacavir (ABC)/lamivudine (3TC); ABC 600 mg/3TC 300 mg tablet, once a day; Other Names: Epzicom, Kivexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) < 200 Copies/mL Through Week 48 Based on Time to Loss of Virologic Response (TLOVR) Algorithm	The percentage of participants with HIV-1 RNA < 200 copies/mL based on TLOVR algorithm at Week 48 was summarized. Participants were considered nonresponders in the TLOVR analysis if they experienced virologic rebound prior to or at Week 48, discontinued study before Week 48, or added a new antiretroviral (ARV) agent prior to completion of the study. Virologic rebound was defined as 2 consecutive HIV-1 RNA values >= 200 copies/mL or the last HIV-1 RNA value >= 200 copies/mL followed by discontinuation from the study.	Baseline to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 200 Copies/mL Through Week 48	The percentage of participants with PVR for HIV-1 RNA cutoff at 200 copies/mL at Week 48 was summarized. Pure virologic response was the percentage of subjects who did not have a virologic rebound. Virologic rebound was defined as two consecutive HIV-1 RNA values >= 200 copies/mL or the last HIV-1 RNA value >= 200 copies/mL followed by discontinuation from the study.	Baseline to 48 weeks
Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 50 Copies/mL Through Week 48	The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 48 was summarized. Pure virologic response was the proportion of participants who did not have a virologic rebound. Virologic rebound was defined as two consecutive HIV-1 RNA values >= 50 copies/mL or the last HIV-1 RNA value >= 50 copies/mL followed by discontinuation from the study.	Baseline to 48 weeks
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA < 200 copies/mL at Week 48 was summarized.	48 weeks
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 summarized.	48 weeks
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Calculated Creatinine Clearance (CLcr) Using Ideal Body Weight by Cockcroft-Gault Method at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Estimated Glomerular Filtration Rate (eGFR) by Modified Diet in Renal Disease (MDRD) at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Fasting Glucose at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Fasting Lipid Parameters at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Ratio of Fasting Total Cholesterol Over High-density Lipoprotein (HDL) Cholesterol at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline C-Reactive Protein at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Fibrinogen at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks
Change From Baseline Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-alpha (TNF-alpha) at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Todd Fralich, MD, Gilead Sciences

Publications and helpful links

General Publications

• Campo R, DeJesus E, Bredeek UF, Henry K, Khanlou H, Logue K, Brinson C, Benson P, Dau L, Wang H, White K, Flaherty J, Fralich T, Guyer B, Piontkowsky D. SWIFT: prospective 48-week study to evaluate efficacy and safety of switching to emtricitabine/tenofovir from lamivudine/abacavir in virologically suppressed HIV-1 infected patients on a boosted protease inhibitor containing antiretroviral regimen. Clin Infect Dis. 2013 Jun;56(11):1637-45. doi: 10.1093/cid/cis1203. Epub 2013 Jan 29. Erratum In: Clin Infect Dis. 2013 Sep;57(5):779.

Helpful Links

• Gilead Website
• Click here for more information about Truvada

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): March 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: July 25, 2008
• First Submitted That Met QC Criteria: July 28, 2008
• First Posted (ESTIMATE): July 29, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): May 28, 2012
• Last Update Submitted That Met QC Criteria: May 22, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: HIV; HIV 1
• 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; 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; Tenofovir; Emtricitabine; Lamivudine; Abacavir
• Other Study ID Numbers: GS-US-164-0216