Mechanisms of Lipodystrophy in HIV-Infected Pateints

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Mecahnisms of Lipodystrophy in HIV-Infected Patients

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nelfinavir
* Drug: Efavirenz


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nelfinavir (Viracept)<br> | Drug: Nelfinavir<br> <br> * Other names: Viracept;|
| Active Comparator: Efavirenz (Sustiva)<br> | Drug: Efavirenz<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Lipodystrophy, Treatment Experienced