Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals.
The use of highly active anti-retroviral therapy (HAART) is associated with long-term adverse metabolic events including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of the present study was to prospectively examine the mechanism of HAART-induced hyperlipidemia in HIV-seropositive, HAART-naive men prior to the development of frank lipodystrophy. Patient's (n = 13) weight, BMI, lean mass, and percent fat mass, waist circumference did not change after 8 weeks of treatment with HAART. Plasma FFA concentration was already elevated in HAART-naive patients compared to healthy, untreated, HIV negative control individuals and was further increased after 8 weeks of HAART in the former. Insulin-mediated suppression of plasma FFA concentrations was impaired both prior to and following introduction of HAART, compared to healthy, matched controls. VLDL-apoB and VLDL-TG concentrations rose significantly from normal levels after HAART. Compared to healthy control subjects, VLDL fractional catabolic rate and clearance in HIV-seropositive individuals was reduced by approximately 40%, a defect that was not corrected after HAART. The increase in VLDL after HAART was explained by an increase of VLDL-apoB and VLDL-TG secretion towards normal while the impaired VLDL clearance remained unchanged. We conclude that elevation of circulating VLDL early in the course of HAART is caused by the combination of impaired VLDL clearance already present in HAART-naive HIV-seropositive patients and HAART-mediated increase in VLDL secretion. These changes occur concomitantly with an elevation of plasma free fatty acids but before significant change in body composition.
Carpentier
André
A
The Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Que., Canada.
Patterson
Bruce W
BW
Uffelman
Kristine D
KD
Salit
Irving
I
Lewis
Gary F
GF
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced*; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D007262:Infusions, Intravenous; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001786:Blood Glucose; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D005947:Glucose