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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00109603
• Other study ID #: ACTG A5206
• Status: Completed
• Phase: N/A
• First received: April 29, 2005
• Last updated: October 26, 2012
• Start date: May 2005
• Est. completion date: November 2007

Study information

• Verified date: October 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: November 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyslipidemia
• Dyslipidemias
• HIV Infections
• Hypercholesterolemia
• Hyperlipidemia
• Hyperlipidemias
• Hypertriglyceridemia

Intervention

Drug:
• Tenofovir disoproxil fumarate

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico	San Juan
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland, Institute of Human Virology	Baltimore	Maryland
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	University of Colorado Health Sciences Center, Denver	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas, Galveston	Galveston	Texas
United States	Indiana University Hospital	Indianapolis	Indiana
United States	Methodist Hospital of Indiana	Indianapolis	Indiana
United States	Wishard Hospital	Indianapolis	Indiana
United States	University of Southern California	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Beth Israel Medical Center	New York	New York
United States	NYU/Bellevue	New York	New York
United States	University of Pennsylvania, Philadelphia	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California, San Diego Antiviral Research Center	San Diego	California
United States	Washington University (St. Louis)	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (6)

Dubé 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. — View Citation

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. — View Citation

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

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. Review. — View Citation

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

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 Ju — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting non-HDL cholesterol at baseline and Weeks 12, 16, and 28
Secondary	Fasting HDL, total cholesterol, and triglycerides
Secondary	direct LDL by ultracentrifugation
Secondary	viral load, CD4 count, and other clinical and laboratory measures

External Links

•   Click here for more information on hyperlipidemia
•   Click here for more information on tenofovir disoproxil fumarate
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