Mechanisms of Lipodystrophy in HIV-Infected Pateints

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.

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.