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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


Phase 4
18 Years
N/A
Not Enrolling
Both
HIV Infection

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Trial Information

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 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.


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

Type of Study:

Interventional

Study Design:

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

Outcome 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

Outcome Description:

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.

Outcome Time Frame:

Baseline to 48 weeks

Safety Issue:

No

Principal Investigator

Todd Fralich, MD

Investigator Role:

Study Director

Investigator Affiliation:

Gilead Sciences

Authority:

United States: Institutional Review Board

Study ID:

GS-US-164-0216

NCT ID:

NCT00724711

Start Date:

July 2008

Completion Date:

April 2011

Related Keywords:

  • HIV Infection
  • HIV
  • HIV 1
  • HIV Infections
  • Acquired Immunodeficiency Syndrome

Name

Location

Henry Ford HospitalDetroit, Michigan  48202
Medical College of WisconsinMilwaukee, Wisconsin  53226
University of Rochester Medical CenterRochester, New York  14642
Baylor University Medical CenterDallas, Texas  75246
Hennepin County Medical CenterMinneapolis, Minnesota  
University of FloridaGainesville, Florida  32610-0277
University of LouisvilleLouisville, Kentucky  40202
University of MiamiMiami, Florida  33136
Wake Forest University School of MedicineWinston-Salem, North Carolina  27157-1023
Clinical Pharmacology ServicesTampa, Florida  
Kaiser PermanenteDenver, Colorado  80204-4507
Saint Michael's Medical CenterNewark, New Jersey  07102
UT Southwestern Medical Center at DallasDallas, Texas  75390
Abbott Northwestern HospitalMinneapolis, Minnesota  55430
Howard Brown Health CenterChicago, Illinois  60613
Health For Life Clinic, PLLCLittle Rock, Arkansas  72207
Vista Medical PartnersBeverly Hills, California  90210
AHFBeverly Hills, California  90211
Pacific Oaks Medical GroupBeverly Hills, California  90211
Center for Special ImmunologyFountain Valley, California  92708
Living Hope Clinical FoundationLong Beach, California  90813
Jeffrey Goodman Special Care ClinicLos Angeles, California  90028
Anthony M Mills, MDLos Angeles, California  90069
Peter J. Ruane, MD, Inc.Los Angeles, California  90036
Orange Coast Medical GroupNewport Beach, California  92663
Tarzana Treatment CenterNorthridge, California  91324
Alameda County Medical CenterOakland, California  94602
Health Management Institute, Inc.San Francisco, California  94114
Metropolis MedicalSan Francisco, California  94115
Blick Medical AssociatesNorwalk, Connecticut  06851
Gary Richmond, MD, PA, Inc.Fort Lauderdale, Florida  33316
Life Way Inc.Fort Lauderdale, Florida  33308
Therafirst Medical CentersFort Lauderdale, Florida  33308
HIV Clinical ResearchFt. Lauderdale, Florida  33311
Biogenomx Research Institute, LLCFt. Lauderdale, Florida  33306
The Kinder Medical GroupMiami, Florida  33133
Community Health of South Florida Inc.Miami, Florida  33190
South Florida Infectious Diseases and Tropical Medicine CenterMiami, Florida  33176
Wohlfeiler, Piperato and Associates, LLCMiami Beach, Florida  33139
Orlando Immunology CenterOrlando, Florida  32803
Infectious Diseases Associates of NW FLPensacola, Florida  32504
Associates in Infectious DiseasesPort St. Lucie, Florida  34952
Barry M. Rodwick, M.D.Safety Harbor, Florida  34695
Infectious Disease Research Institute, Inc.Tampa, Florida  33614
USF HealthTampa, Florida  33602
Infectious Disease SolutionsAtlanta, Georgia  30309
Atlanta Infectious Disease Group, PCAtlanta, Georgia  30309
Family Healthcare of Atlanta PCAtlanta, Georgia  30318
Chatham County Health DepartmentSavannah, Georgia  31401
NorthStar Medical CenterChicago, Illinois  60657
Chase Brexton Health ServicesBaltimore, Maryland  21201
MetroWest Medical CenterFramingham, Massachusetts  01702
The Research InstituteSpringfield, Massachusetts  01107
Community Research Initiative of New England - WESTSpringfield, Massachusetts  01107
Be Well Medical CenterBerkley, Michigan  48072
Michigan State University, College of Osteopathic MedicineEast Lansing, Michigan  48824
St. John Hospital Internal Medicine Clinic - Mack Office BuildingGrosse Point Woods, Michigan  48236
ID Associates, PAHillsborough, New Jersey  08844
South Jersey Infectious DiseaseSomers Point, New Jersey  08244
Upstate Infectious Diseases AssociatesAlbany, New York  23309
Greiger ClinicMount Vernon, New York  10550
Ricky K. Hsu, MD, PCNew York, New York  10011
AIDS Community Health CenterRochester, New York  14604
ID Consultants, P.A.Charlotte, North Carolina  28209
East Carolina University The Brody School of MedicineGreenville, North Carolina  27858
Summa Health System Care CenterAkron, Ohio  44394
Central Texas Clinical ResearchAustin, Texas  78705
North Texas Inf. Disease ConsultantsDallas, Texas  75246
Tarrant County Infectious Disease AssociatesFort Worth, Texas  76104
Valley AIDS CounselHarlingen, Texas  78550
Gordon E. Crofoot, MD, PAHouston, Texas  77098
Therapeutic Concepts, PAHouston, Texas  77004
Daniel Coulston, MDSpokane, Washington  99204