Safety and Efficacy Study of Switching From Epzicom to Truvada

HIV Infection Clinical Trial

— SWIFT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00724711
• Other study ID #: GS-US-164-0216
• Status: Completed
• Phase: Phase 4
• First received: July 25, 2008
• Last updated: May 22, 2012
• Start date: July 2008
• Est. completion date: April 2011

Study information

• Verified date: May 2012
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: April 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

Drug:
• emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)
FTC 200 mg/TDF 300 mg tablet, once a day
• abacavir (ABC)/lamivudine (3TC)
ABC 600 mg/3TC 300 mg tablet, once a day

Locations

Country	Name	City	State
Canada	Clinique Du Quartier Latin	Montreal	Quebec
Canada	Canadian Immunodeficiency Research Collaborative Incorporated	Toronto	Ontario
Canada	CascAids Research	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Puerto Rico	Instituto de Investigacion Cientifica del Sur	Ponce
Puerto Rico	Clinical Research Puerto Rico Inc	San Juan
Puerto Rico	University of Puerto Rico	San Juan
United States	Summa Health System Care Center	Akron	Ohio
United States	Upstate Infectious Diseases Associates	Albany	New York
United States	Atlanta Infectious Disease Group, PC	Atlanta	Georgia
United States	Family Healthcare of Atlanta PC	Atlanta	Georgia
United States	Infectious Disease Solutions	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Chase Brexton Health Services	Baltimore	Maryland
United States	Be Well Medical Center	Berkley	Michigan
United States	AHF	Beverly Hills	California
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	Vista Medical Partners	Beverly Hills	California
United States	ID Consultants, P.A.	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	NorthStar Medical Center	Chicago	Illinois
United States	Baylor University Medical Center	Dallas	Texas
United States	North Texas Inf. Disease Consultants	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Kaiser Permanente	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Michigan State University, College of Osteopathic Medicine	East Lansing	Michigan
United States	Gary Richmond, MD, PA, Inc.	Fort Lauderdale	Florida
United States	Life Way Inc.	Fort Lauderdale	Florida
United States	Therafirst Medical Centers	Fort Lauderdale	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	Center for Special Immunology	Fountain Valley	California
United States	MetroWest Medical Center	Framingham	Massachusetts
United States	Biogenomx Research Institute, LLC	Ft. Lauderdale	Florida
United States	HIV Clinical Research	Ft. Lauderdale	Florida
United States	East Carolina University The Brody School of Medicine	Greenville	North Carolina
United States	St. John Hospital Internal Medicine Clinic - Mack Office Building	Grosse Point Woods	Michigan
United States	Valley AIDS Counsel	Harlingen	Texas
United States	ID Associates, PA	Hillsborough	New Jersey
United States	Gordon E. Crofoot, MD, PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	University of Florida	Jacksonville	Florida
United States	Health For Life Clinic, PLLC	Little Rock	Arkansas
United States	Living Hope Clinical Foundation	Long Beach	California
United States	Anthony M Mills, MD	Los Angeles	California
United States	Jeffrey Goodman Special Care Clinic	Los Angeles	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Community Health of South Florida Inc.	Miami	Florida
United States	South Florida Infectious Diseases and Tropical Medicine Center	Miami	Florida
United States	The Kinder Medical Group	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Greiger Clinic	Mount Vernon	New York
United States	Ricky K. Hsu, MD, PC	New York	New York
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Orange Coast Medical Group	Newport Beach	California
United States	Tarzana Treatment Center	Northridge	California
United States	Blick Medical Associates	Norwalk	Connecticut
United States	Alameda County Medical Center	Oakland	California
United States	Orlando Immunology Center	Orlando	Florida
United States	Infectious Diseases Associates of NW FL	Pensacola	Florida
United States	Associates in Infectious Diseases	Port St. Lucie	Florida
United States	AIDS Community Health Center	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	Barry M. Rodwick, M.D.	Safety Harbor	Florida
United States	Health Management Institute, Inc.	San Francisco	California
United States	Metropolis Medical	San Francisco	California
United States	Chatham County Health Department	Savannah	Georgia
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Daniel Coulston, MD	Spokane	Washington
United States	Community Research Initiative of New England - WEST	Springfield	Massachusetts
United States	The Research Institute	Springfield	Massachusetts
United States	Clinical Pharmacology Services	Tampa	Florida
United States	Infectious Disease Research Institute, Inc.	Tampa	Florida
United States	USF Health	Tampa	Florida
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	Change From Baseline Fasting Glucose at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks	No
Secondary	Change From Baseline Fasting Lipid Parameters at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks	No
Secondary	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	No
Secondary	Change From Baseline C-Reactive Protein at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks	No
Secondary	Change From Baseline Fibrinogen at Week 48	Change = Week 48 value minus baseline value	Baseline to 48 weeks	No
Secondary	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	No

External Links

•   Click here for more information about Truvada
•   Gilead Website