Safety and Efficacy Study of Switching From Epzicom to Truvada

Phase 4

Completed

Conditions: HIV Infection

Interventions: Drug: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)
Drug: abacavir (ABC)/lamivudine (3TC)

Registration Number: NCT00724711

Lead Sponsor: Gilead Sciences

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 312

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FTC/TDF (Truvada [TVD]) + PI/r	emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)	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.
ABC/3TC + PI/r	abacavir (ABC)/lamivudine (3TC)	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.

Primary Outcome Measures

Name	Time	Method
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	Baseline to 48 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	48 weeks	The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was summarized.
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline Calculated Creatinine Clearance (CLcr) Using Ideal Body Weight by Cockcroft-Gault Method at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline Estimated Glomerular Filtration Rate (eGFR) by Modified Diet in Renal Disease (MDRD) at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline Fasting Glucose at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 200 Copies/mL Through Week 48	Baseline to 48 weeks	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.
Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 50 Copies/mL Through Week 48	Baseline to 48 weeks	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.
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48	48 weeks	The percentage of participants with HIV-1 RNA \< 200 copies/mL at Week 48 was summarized.
Change From Baseline Fasting Lipid Parameters at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline Ratio of Fasting Total Cholesterol Over High-density Lipoprotein (HDL) Cholesterol at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline C-Reactive Protein at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline Fibrinogen at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value
Change From Baseline Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-alpha (TNF-alpha) at Week 48	Baseline to 48 weeks	Change = Week 48 value minus baseline value

Trial Locations

Locations (80): Peter J. Ruane, MD, Inc.
🇺🇸
Los Angeles, California, United States
Anthony M Mills, MD
🇺🇸
Los Angeles, California, United States
Orange Coast Medical Group
🇺🇸
Newport Beach, California, United States
Blick Medical Associates
🇺🇸
Norwalk, Connecticut, United States
Life Way Inc.
🇺🇸
Fort Lauderdale, Florida, United States
Therafirst Medical Centers
🇺🇸
Fort Lauderdale, Florida, United States
Gary Richmond, MD, PA, Inc.
🇺🇸
Fort Lauderdale, Florida, United States
Saint Michael's Medical Center
🇺🇸
Newark, New Jersey, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
UT Southwestern Medical Center at Dallas
🇺🇸
Dallas, Texas, United States
Therapeutic Concepts, PA
🇺🇸
Houston, Texas, United States
The Kinder Medical Group
🇺🇸
Miami, Florida, United States
University of Miami
🇺🇸
Miami, Florida, United States
South Florida Infectious Diseases and Tropical Medicine Center
🇺🇸
Miami, Florida, United States
Community Health of South Florida Inc.
🇺🇸
Miami, Florida, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Health Management Institute, Inc.
🇺🇸
San Francisco, California, United States
Metropolis Medical
🇺🇸
San Francisco, California, United States
Barry M. Rodwick, M.D.
🇺🇸
Safety Harbor, Florida, United States
Infectious Disease Research Institute, Inc.
🇺🇸
Tampa, Florida, United States
The Research Institute
🇺🇸
Springfield, Massachusetts, United States
Michigan State University, College of Osteopathic Medicine
🇺🇸
East Lansing, Michigan, United States
Atlanta Infectious Disease Group, PC
🇺🇸
Atlanta, Georgia, United States
Chase Brexton Health Services
🇺🇸
Baltimore, Maryland, United States
Instituto de Investigacion Cientifica del Sur
🇵🇷
Ponce, Puerto Rico
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Howard Brown Health Center
🇺🇸
Chicago, Illinois, United States
Upstate Infectious Diseases Associates
🇺🇸
Albany, New York, United States
Ricky K. Hsu, MD, PC
🇺🇸
New York, New York, United States
CascAids Research
🇨🇦
Toronto, Ontario, Canada
USF Health
🇺🇸
Tampa, Florida, United States
AIDS Community Health Center
🇺🇸
Rochester, New York, United States
Infectious Diseases Associates of NW FL
🇺🇸
Pensacola, Florida, United States
MetroWest Medical Center
🇺🇸
Framingham, Massachusetts, United States
South Jersey Infectious Disease
🇺🇸
Somers Point, New Jersey, United States
Associates in Infectious Diseases
🇺🇸
Port St. Lucie, Florida, United States
Chatham County Health Department
🇺🇸
Savannah, Georgia, United States
NorthStar Medical Center
🇺🇸
Chicago, Illinois, United States
ID Associates, PA
🇺🇸
Hillsborough, New Jersey, United States
Greiger Clinic
🇺🇸
Mount Vernon, New York, United States
Abbott Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Clinical Pharmacology Services
🇺🇸
Tampa, Florida, United States
Infectious Disease Solutions
🇺🇸
Atlanta, Georgia, United States
Family Healthcare of Atlanta PC
🇺🇸
Atlanta, Georgia, United States
Be Well Medical Center
🇺🇸
Berkley, Michigan, United States
ID Consultants, P.A.
🇺🇸
Charlotte, North Carolina, United States
Community Research Initiative of New England - WEST
🇺🇸
Springfield, Massachusetts, United States
East Carolina University The Brody School of Medicine
🇺🇸
Greenville, North Carolina, United States
Summa Health System Care Center
🇺🇸
Akron, Ohio, United States
Wake Forest University School of Medicine
🇺🇸
Winston-Salem, North Carolina, United States
Valley AIDS Counsel
🇺🇸
Harlingen, Texas, United States
Gordon E. Crofoot, MD, PA
🇺🇸
Houston, Texas, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
Health For Life Clinic, PLLC
🇺🇸
Little Rock, Arkansas, United States
Vista Medical Partners
🇺🇸
Beverly Hills, California, United States
Center for Special Immunology
🇺🇸
Fountain Valley, California, United States
AHF
🇺🇸
Beverly Hills, California, United States
Living Hope Clinical Foundation
🇺🇸
Long Beach, California, United States
Jeffrey Goodman Special Care Clinic
🇺🇸
Los Angeles, California, United States
Tarzana Treatment Center
🇺🇸
Northridge, California, United States
Alameda County Medical Center
🇺🇸
Oakland, California, United States
Kaiser Permanente
🇺🇸
Denver, Colorado, United States
Biogenomx Research Institute, LLC
🇺🇸
Ft. Lauderdale, Florida, United States
HIV Clinical Research
🇺🇸
Ft. Lauderdale, Florida, United States
University of Florida
🇺🇸
Jacksonville, Florida, United States
Wohlfeiler, Piperato and Associates, LLC
🇺🇸
Miami Beach, Florida, United States
Orlando Immunology Center
🇺🇸
Orlando, Florida, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
St. John Hospital Internal Medicine Clinic - Mack Office Building
🇺🇸
Grosse Point Woods, Michigan, United States
Central Texas Clinical Research
🇺🇸
Austin, Texas, United States
Tarrant County Infectious Disease Associates
🇺🇸
Fort Worth, Texas, United States
North Texas Inf. Disease Consultants
🇺🇸
Dallas, Texas, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of British Columbia
🇨🇦
Vancouver, British Columbia, Canada
Canadian Immunodeficiency Research Collaborative Incorporated
🇨🇦
Toronto, Ontario, Canada
Daniel Coulston, MD
🇺🇸
Spokane, Washington, United States
Clinique Du Quartier Latin
🇨🇦
Montreal, Quebec, Canada
University of Puerto Rico
🇵🇷
San Juan, Puerto Rico
Clinical Research Puerto Rico Inc
🇵🇷
San Juan, Puerto Rico
Pacific Oaks Medical Group
🇺🇸
Beverly Hills, California, United States