Mechanisms of Lipodystrophy in HIV-Infected Pateints

Mecahnisms of Lipodystrophy in HIV-Infected Patients

The metabolic and molecular basis of lipodystrophy syndrome in HIV-infected patients is not known. Whether besides protease inhibitors, other antiretroviral drugs, HIV infection and reduction in viral load contribute to the development of lipodystrophy syndrome is not clear.

The project therefore has the following aims: 1) to characterize metabolic abnormalities and changes in body fat distribution, 2) to develop objective criteria for defining the syndrome and to ascertain prognostic indicators and 3) to elucidate the molecular basis of the lipodystrophy syndrome in HIV-infected patients.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Efavirenz; Drug: Nelfinavir

Detailed Description

A 2-year long prospective, randomized, double blind, placebo-controlled study in 200 asymptomatic HIV (+) patients to compare two equally effective antiretroviral regimens, one with and the other without a protease inhibiotor. We will study body fat distribution by anthropometry and magnetic resonance imaging and will measure insulin sensitivity (in a subset of patients), plasma lipoproteins, glucose tolerance and other metabolic variables. We will study expression of an array of adipocyte specific proteins/transcription factors involved in adipocyte differentiation, insulin action and lipoprotein metabolism in fat biopsy samples obtained before and after institution of therapy.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas 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:

• HIV Positive
• No previous antiviral therapy
• 18 to 70 years of age

Exclusion Criteria:

• Patients with opportunistic infections or AIDS.
• Active intravenous drug users.
• Patients on corticosteroids, androgens, lipid-lowering drugs, anti-fungal medications, dehydroepiandrosterone, oxandrolone, megace.
• Patients with diabetes mellitus.
• Patients with moderate to heavy alcohol consumption ( greater than 15 drinks per week).
• Pregnant or premenopausal women, unless surgically sterilized or highly unlikely to conceive (defined as women taking oral contraceptives, using barrier protection during intercourse or with a copper intrauterine device in place for > 3 months without complaints and a negative serum or urine pregnancy test within 30 days of study entry).
• Acute or chronic liver diseases; elevations of liver transaminases by more than two and one half times above the upper limits of normal ( SGOT > 105 U/L, SGPT > 120 U/L, ) or a total bilirubin of > 1.5mg/dL.
• Anemia (hematocrit <32%).
• Abnormal thyroid function tests.
• Weight loss >10% from baseline in the past year.
• Recent (within the past year), history of suicide attempt.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nelfinavir (Viracept)	Drug: Nelfinavir; Other Names: Viracept
Active Comparator: Efavirenz (Sustiva)	Drug: Efavirenz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of Drug Regimens on Serum Triglycerides.	12 and 24 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Bristol-Myers Squibb; GlaxoSmithKline
• Investigators: Principal Investigator: Abhimanyu Garg, M.D., University of Texas Southwestern Medical Center Dallas

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: April 4, 2007
• First Submitted That Met QC Criteria: April 5, 2007
• First Posted (Estimate): April 6, 2007

Study Record Updates

• Last Update Posted (Actual): July 18, 2019
• Last Update Submitted That Met QC Criteria: May 8, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: HIV; Treatment Experienced; Lipodystrophy
• 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; 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; Nelfinavir; Efavirenz
• Other Study ID Numbers: R01-56583