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Influence of protease inhibitor therapy on lipoprotein metabolism.

Abstract：

OBJECTIVES:Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper- and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV-infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options. DESIGN:We investigated prospectively, in 19 subsequent HIV-positive male patients (mean age 42 +/- 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7-40) weeks. 12 patients were treatment-naive; 7 had already NRTI medication at baseline. RESULTS:Total cholesterol increased by 28 mg dL-1 (95% CI: + 7 to + 48, baseline 158 +/- 53, P = 0.01), triglycerides increased by 96 mg dL-1 (+ 22 to + 170, baseline 152 +/- 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL-1 (+ 9 to + 31, baseline 33 +/- 21, P = 0.001), VLDL triglycerides increased by 86 mg dL-1 (+ 22 to + 150, baseline 128 +/- 91, P = 0. 01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 +/- 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (-0.02 to -0.09, baseline 0.47 +/- 0.11, P = 0.005). (Conversion factors, mg dL-1 to mmol L-1: 0.0259 for cholesterol, 0.0114 for triglycerides.) CONCLUSIONS:The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride-containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.

journal_name

J Intern Med

journal_title

Journal of internal medicine

authors

Berthold HK,Parhofer KG,Ritter MM,Addo M,Wasmuth JC,Schliefer K,Spengler U,Rockstroh JK

doi

10.1046/j.1365-2796.1999.00615.x

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

567-75

issue

eissn

0954-6820

issn

1365-2796

pii

jim615

journal_volume

246

pub_type

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Influence of protease inhibitor therapy on lipoprotein metabolism.