Effect of Tenofovir Disoproxil Fumarate on Lipid Levels in HIV Infected Adults on Stable Anti-HIV Drug Therapy - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00109603

Purpose

The purpose of this study is to determine the effect of the anti-HIV drug tenofovir disoproxil fumarate (TDF) on lipid levels in HIV infected adults on stable anti-HIV drug therapy.

Study hypothesis: The addition of TDF to stable background antiretroviral therapy in HIV infected individuals with dyslipidemia will result in a reduction of non-HDL after 12 weeks of treatment.

Condition	Intervention
HIV Infections Dyslipidemia Hyperlipidemia Hypercholesterolemia Hypertriglyceridemia	Drug: Tenofovir disoproxil fumarate

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	A Pilot Study to Determine the Impact on Dyslipidemia of the Addition of Tenofovir to Stable Background Antiretroviral Therapy in HIV-Infected Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency hypercholesterolemia

MedlinePlus related topics: Cholesterol HIV/AIDS HIV/AIDS Medicines Triglycerides

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Fasting non-HDL cholesterol at baseline and Weeks 12, 16, and 28

Secondary Outcome Measures:

Fasting HDL, total cholesterol, and triglycerides
direct LDL by ultracentrifugation
viral load, CD4 count, and other clinical and laboratory measures

Estimated Enrollment:	56
Study Start Date:	May 2005
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Use of highly active antiretroviral therapy (HAART) has resulted in significant reductions in morbidity and mortality among HIV infected people. However, significant adverse effects, including dyslipidemia, have been associated with HAART. Dyslipidemia may cause elevations in serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations, as well as a decrease in high-density lipoprotein (HDL) concentrations. Dyslipidemia is of particular concern for patients receiving HAART because the condition is associated with increased risk for cardiovascular events. TDF is an antiretroviral that has exhibited favorable lipid effects in several studies in HIV infected people, but the mechanism for the observed lipid-lowering effect of TDF is unknown. This study will evaluate the efficacy of TDF on lowering non-HDL in HIV infected adults currently on stable HAART. HAART itself will not be provided by this study.

This study will last 32 weeks. Participants will be randomly assigned to one of two study arms. Arm A participants will receive 12 weeks of TDF daily, 4 weeks of no TDF, 12 weeks of placebo daily, then 4 weeks of no TDF. Arm B participants will receive 12 weeks of placebo daily, 4 weeks of no TDF, 12 weeks of TDF daily, then 4 weeks of no TDF. Participants will continue to take their currently prescribed stable HAART regimen for the duration of the study. There will be 13 study visits over the 32 weeks of the study. Clinical assessments will occur at all visits; blood and urine collection will occur at most visits.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infected
HIV viral load less than 400 copies/ml within 28 days prior to study entry
Treatment with stable HAART for at least 90 days prior to study entry. Patients who have taken TDF, didanosine, unboosted atazanavir, or adefovir within 90 days prior to study entry are not eligible.
Fasting triglycerides of 150 mg/dl or greater AND less than 1000 mg/dl within 28 days prior to study entry or fasting non-HDL cholesterol 100 mg/dl or greater AND less than 250 mg/dl within 28 days prior to study
Hepatitis B virus surface antigen negative within 6 months prior to study entry
Have adhered to a lipid-lowering diet and exercise program for at least 28 days prior to study screening, and willing to continue both for the duration of the study
Willing to continue any current use of hormone replacement therapy or oral contraceptives for the duration of the study. Participants must have been on a stable dose of these medications for at least 28 days prior to study entry to be eligible.
Willing to use acceptable means of contraception

Exclusion Criteria:

Any lipid-lowering agents within 28 days prior to study entry
Nephrotoxins, such as foscarnet and amphotericin B, within 28 days prior to study entry
Systemic cancer chemotherapy within 60 days prior to study entry
Hormonal anabolic therapies or systemic steroids within 6 months prior to study entry
Allergy or sensitivity to the study drug or its formulation
Uncontrolled diabetes, as defined by the protocol, within 28 days prior to study entry
Current hypothyroidism which has been treated for less than 28 days prior to study entry
History of coronary heart disease, known atherosclerotic disease, cerebrovascular disease, peripheral vascular disease, abdominal aortic aneurysm, or arterial blockage
Any acute illness within 28 days prior to study entry that, in the opinion of the investigator, may interfere with the study
Current drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00109603

Locations

United States, California
University of Southern California
Los Angeles, California, United States, 90033-1079
University of California, San Diego Antiviral Research Center
San Diego, California, United States, 92103
United States, Colorado
University of Colorado Health Sciences Center, Denver
Denver, Colorado, United States, 80262-3706
United States, Florida
University of Miami
Miami, Florida, United States, 33136-1013
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202-5250
Methodist Hospital of Indiana
Indianapolis, Indiana, United States, 46202-5250
Wishard Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8106
United States, Missouri
Washington University (St. Louis)
St. Louis, Missouri, United States, 63108-2138
United States, New York
NYU/Bellevue
New York, New York, United States, 10016-6481
Beth Israel Medical Center
New York, New York, United States, 10003
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0405
Case Western Reserve University
Cleveland, Ohio, United States, 44106-5083
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109-1998
United States, Pennsylvania
University of Pennsylvania, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213-2582
United States, Texas
University of Texas, Galveston
Galveston, Texas, United States, 77555-0435
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Judith Aberg, MD	New York University Medical Center
Study Chair:	Marisa Tungsiripat, MD	The Cleveland Clinic

More Information

Additional Information:

Click here for more information on tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information on hyperlipidemia This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Tungsiripat M, Kitch D, Glesby MJ, Gupta SK, Mellors JW, Moran L, Jones L, Alston-Smith B, Rooney JF, Aberg JA. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS. 2010 May 21; [Epub ahead of print]

Dube MP, Stein JH, Aberg JA, Fichtenbaum CJ, Gerber JG, Tashima KT, Henry WK, Currier JS, Sprecher D, Glesby MJ; Adult AIDS Clinical Trials Group Cardiovascular Subcommittee; HIV Medical Association of the Infectious Disease Society of America. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003 Sep 1;37(5):613-27. Epub 2003 Aug 15. Review. No abstract available.

Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005 Jan 6;352(1):48-62. Review. No abstract available.

Martinez E, Tuset M, Milinkovic A, Miro JM, Gatell JM. Management of dyslipidaemia in HIV-infected patients receiving antiretroviral therapy. Antivir Ther. 2004 Oct;9(5):649-63. Review.

Mehta N, Reilly M. Atherosclerotic Cardiovascular Disease Risk in the HAART-Treated HIV-1 Population. HIV Clin Trials. 2005 Jan-Feb;6(1):5-24.

Stein JH. Managing cardiovascular risk in patients with HIV infection. J Acquir Immune Defic Syndr. 2005 Feb 1;38(2):115-23. Review.

Responsible Party:	Rona Siskind, DAIDS
ClinicalTrials.gov Identifier:	NCT00109603 History of Changes
Other Study ID Numbers:	ACTG A5206
Study First Received:	April 29, 2005
Last Updated:	June 7, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Experienced
TDF

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Hypercholesterolemia
Hyperlipidemias
Hypertriglyceridemia
Dyslipidemias
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

Lipid Metabolism Disorders
Metabolic Diseases
Tenofovir disoproxil
Tenofovir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 12, 2012