Clinical trial NCT00724711: Safety and Efficacy Study of Switching From Epzicom to Truvada
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: HIV
HIV 1
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-07-29
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline to 48 weeks
Secondary outcomes:
measure: Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 200 Copies/mL Through Week 48
timeFrame: Baseline to 48 weeks
measure: Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 50 Copies/mL Through Week 48
timeFrame: Baseline to 48 weeks
measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48
timeFrame: 48 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: 48 weeks
measure: Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Calculated Creatinine Clearance (CLcr) Using Ideal Body Weight by Cockcroft-Gault Method at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Estimated Glomerular Filtration Rate (eGFR) by Modified Diet in Renal Disease (MDRD) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Fasting Glucose at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Fasting Lipid Parameters at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Ratio of Fasting Total Cholesterol Over High-density Lipoprotein (HDL) Cholesterol at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline C-Reactive Protein at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Fibrinogen at Week 48
timeFrame: Baseline to 48 weeks
measure: Change From Baseline Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-alpha (TNF-alpha) at Week 48
timeFrame: Baseline to 48 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Health For Life Clinic, PLLC
state: Arkansas
city: Beverly Hills
country: United States
facility: Vista Medical Partners
state: California
city: Beverly Hills
country: United States
facility: AHF
state: California
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Fountain Valley
country: United States
facility: Center for Special Immunology
state: California
city: Long Beach
country: United States
facility: Living Hope Clinical Foundation
state: California
city: Los Angeles
country: United States
facility: Jeffrey Goodman Special Care Clinic
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony M Mills, MD
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Northridge
country: United States
facility: Tarzana Treatment Center
state: California
city: Oakland
country: United States
facility: Alameda County Medical Center
state: California
city: San Francisco
country: United States
facility: Health Management Institute, Inc.
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: Denver
country: United States
facility: Kaiser Permanente
state: Colorado
city: Norwalk
country: United States
facility: Blick Medical Associates
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Life Way Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Centers
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA, Inc.
state: Florida
city: Ft. Lauderdale
country: United States
facility: Biogenomx Research Institute, LLC
state: Florida
city: Ft. Lauderdale
country: United States
facility: HIV Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, LLC
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: South Florida Infectious Diseases and Tropical Medicine Center
state: Florida
city: Miami
country: United States
facility: Community Health of South Florida Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates of NW FL
state: Florida
city: Port St. Lucie
country: United States
facility: Associates in Infectious Diseases
state: Florida
city: Safety Harbor
country: United States
facility: Barry M. Rodwick, M.D.
state: Florida
city: Tampa
country: United States
facility: USF Health
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute, Inc.
state: Florida
city: Tampa
country: United States
facility: Clinical Pharmacology Services
state: Florida
city: Atlanta
country: United States
facility: Atlanta Infectious Disease Group, PC
state: Georgia
city: Atlanta
country: United States
facility: Infectious Disease Solutions
state: Georgia
city: Atlanta
country: United States
facility: Family Healthcare of Atlanta PC
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Chicago
country: United States
facility: NorthStar Medical Center
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Chase Brexton Health Services
state: Maryland
city: Framingham
country: United States
facility: MetroWest Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Community Research Initiative of New England - WEST
state: Massachusetts
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University, College of Osteopathic Medicine
state: Michigan
city: Grosse Point Woods
country: United States
facility: St. John Hospital Internal Medicine Clinic - Mack Office Building
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Hillsborough
country: United States
facility: ID Associates, PA
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Albany
country: United States
facility: Upstate Infectious Diseases Associates
state: New York
city: Mount Vernon
country: United States
facility: Greiger Clinic
state: New York
city: New York
country: United States
facility: Ricky K. Hsu, MD, PC
state: New York
city: Rochester
country: United States
facility: AIDS Community Health Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: ID Consultants, P.A.
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University The Brody School of Medicine
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Akron
country: United States
facility: Summa Health System Care Center
state: Ohio
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Dallas
country: United States
facility: North Texas Inf. Disease Consultants
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Harlingen
country: United States
facility: Valley AIDS Counsel
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot, MD, PA
state: Texas
city: Spokane
country: United States
facility: Daniel Coulston, MD
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Toronto
country: Canada
facility: Canadian Immunodeficiency Research Collaborative Incorporated
state: Ontario
city: Toronto
country: Canada
facility: CascAids Research
state: Ontario
city: Montreal
country: Canada
facility: Clinique Du Quartier Latin
state: Quebec
city: Ponce
country: Puerto Rico
facility: Instituto de Investigacion Cientifica del Sur
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Todd Fralich, MD
role: STUDY_DIRECTOR
References:
citation: 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.