A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy

The Study of Mechanisms of Lipodystrophy in HIV-Infected Patients

HIV infection is a major global health problem. Survival and quality of life for HIV subjects has tremendously improved with the advent of a class of antivirals called protease inhibitors and the utilization of highly active combination therapy. However, such therapy has been associated with a syndrome called lipodystrophy. This lipodystrophy syndrome causes body shape changes; typically thinning and loss of fat from the arms, legs and face, with increased fat appearing in the abdomen and neck. There are also metabolic changes which occur, and subjects can develop increased triglycerides, increased cholesterol and an increased risk for diabetes as indicated by increasing insulin resistance. This study will take HIV positive subjects who have not yet started antiviral medications (treatment naive)and randomly assign them to one of two treatment arms. These treatment arms will be: Sustiva/Zerit/Epivir vs. Viracept/Zerit/Epivir The subjects will be treated and followed for two years and have extensive metabolic testing, skinfold thickness measurements, MRI scans and other measures to determine if and how they are experiencing changes in metabolism or body shape and to discover the mechanism of why this occurs. Understanding the mechanism should allow researchers to design interventions for subjects who have lipodystrophy and strategies to prevent lipodystrophy from occurring to subjects treated with antivirals in the future.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Lipodystrophy
• Intervention / Treatment: Drug: Lamivudine; Drug: Stavudine; Drug: Nelfinavir mesylate; Drug: Efavirenz

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-9103
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CD4 count > 200 cells/mm
• HIV RNA (viral load) <= 100,000 copies/ml
• No previous antiviral therapy

Exclusion Criteria:

• AIDS or opportunistic infections
• Active intravenous drug users
• Use of: corticosteroids, androgens, lipid-lowering drugs, anti-fungal medications, oxandrolone, megace, dehydroepiandrosterone.
• Subjects with diabetes mellitus
• Subjects who consume > 2 alcoholic drinks per day
• Pregnant women, premenopausal women unless adequate birth control is in use.
• Acute or chronic liver diseases, liver enzymes elevations > 2.5 times the upper limit of normal.
• Anemia, an Hct < 35% for men, or < 32% for women.
• Abnormal thyroid function tests.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Masking: Double

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Dr. Abhimanyu Garg, UT Southwestern Medical Center; Dr. Dolores Peterson, UT Southwestern Medical Center; Dr. Ruth Berggren, UT Southwestern Medical Center

Publications and helpful links

General Publications

• Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998 May 7;12(7):F51-8. doi: 10.1097/00002030-199807000-00003.
• Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M. "Buffalo hump" in men with HIV-1 infection. Lancet. 1998 Mar 21;351(9106):867-70. doi: 10.1016/S0140-6736(97)11443-X.
• Hengel RL, Watts NB, Lennox JL. Benign symmetric lipomatosis associated with protease inhibitors. Lancet. 1997 Nov 29;350(9091):1596. doi: 10.1016/s0140-6736(05)64011-1. No abstract available.
• Viraben R, Aquilina C. Indinavir-associated lipodystrophy. AIDS. 1998 Apr 16;12(6):F37-9. doi: 10.1097/00002030-199806000-00001.
• Shaw AJ, McLean KA, Evans BA. Disorders of fat distribution in HIV infection. Int J STD AIDS. 1998 Oct;9(10):595-9. doi: 10.1258/0956462981921189.
• Kotler DP, Rosenbaum K, Wang J, Pierson RN. Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):228-37. doi: 10.1097/00042560-199903010-00003.

Study record dates

Study Major Dates

• Study Start: November 1, 2000
• Study Completion: November 1, 2001

Study Registration Dates

• First Submitted: August 25, 2000
• First Submitted That Met QC Criteria: August 25, 2000
• First Posted (Estimate): August 28, 2000

Study Record Updates

• Last Update Posted (Estimate): March 2, 2010
• Last Update Submitted That Met QC Criteria: March 1, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Insulin resistance; Adipose tissue; Lipoproteins
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Skin Diseases, Metabolic; Lipodystrophy; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Lamivudine; Stavudine; Nelfinavir; Efavirenz
• Other Study ID Numbers: lipod (completed); R01DK056583-01 (U.S. NIH Grant/Contract)