The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B.

Abstract

Plasma low density lipoproteins (LDL) comprise multiple discrete subclasses, differing in size, density, and chemical composition. Gradient gel electrophoresis of LDL has demonstrated three common subclass patterns based on the predominant LDL subclass: large LDL, designated subclass pattern A; small LDL particles, designated subclass pattern B; and an intermediate pattern. Genetic studies have demonstrated that these patterns are inherited, but several lines of evidence suggest that environmental factors are important in the phenotypic expression of the pattern. The LDL B pattern is associated with increased levels of plasma triglyceride, reduced high density lipoprotein (HDL), and obesity. To better define the role of environmental factors on LDL phenotypic expression, we determined LDL patterns in patients with the acquired immunodeficiency syndrome (AIDS), an infection characterized by hypertriglyceridemia and weight loss. Similar to previous studies, plasma triglyceride levels were increased, whereas plasma cholesterol, LDL cholesterol, and HDL cholesterol levels were decreased in the AIDS subjects compared to those in age-matched controls. The percentage of AIDS subjects with the LDL B phenotype was increased 2.5-fold, demonstrating an increased prevalence of the LDL B phenotype in an acquired form of hypertriglyceridemia. For each LDL phenotype in AIDS, serum triglyceride levels were higher than the same phenotypic pattern in controls, with the most marked elevations in triglycerides found in AIDS subjects with the LDL B phenotype. In contrast to what was observed in controls, HDL cholesterol levels were decreased in all AIDS subjects and were unrelated to LDL pattern. Total and LDL cholesterol levels were higher in controls with the LDL B phenotype than in those with the LDL A phenotype, but there was no difference in total and LDL cholesterol in AIDS subjects with LDL B compared to A. On multiple regression analysis in subjects with AIDS, plasma triglyceride levels, age, and HDL cholesterol all contribute to the occurrence of the LDL B phenotype, but elevations in plasma triglyceride levels are the strongest independent predictor. Body mass index was not a predictor of LDL B phenotype in AIDS. These results suggest that disturbances in triglyceride metabolism that are caused by AIDS lead to the appearance of the LDL subclass B phenotype and provide further evidence that environmental or disease states that perturb lipid metabolism can produce an increased prevalence of the LDL B phenotype.

Insulin‐like growth factor‐I–forkhead box O transcription factor 3a counteracts high glucose/tumor necrosis factor‐α‐mediated neuronal damage: Implications for human immunodeficiency virus encephalitis

“…Studies conducted before the widespread use of HAART indicate that HIV infection is associated with increased blood levels of triglycerides and the presence of small, dense low-density lipoprotein (LDL) particles (Grunfeld et al, 1989; Feingold et al, 1993; Shor-Posner et al, 1993). The addition of antiretroviral medications, in particular, the use of protease inhibitors, often leads to the development of insulin resistance and type 2 diabetes mellitus in this already susceptible population (Walli et al, 1998; Carr et al, 1999; Calza et al, 2003; Nishikawa et al, 2003).…”

Metabolic Abnormalities Associated with the Use of Protease Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors

“…The increased TG level has been shown to correlate with elevated interferon-levels [9,12] the host response to viral infection. Lastly, increased TGs have been associated with an increased prevalence of LDL-b phenotype in patients with AIDS [15] . This constellation of changes in HIV infection and AIDS (increased TG, decreased HDL-c and smaller LDL particles) are consistent with a dyslipidemic, proatherogenic profile.…”

Disturbance of Apolipoprotein B100 Containing Lipoprotein Metabolism in Severe Hyperlipidemic and Lipodystrophic HIV Patients on Combined Antiretroviral Therapy: Evidences of Insulin Resistance Effect

“…In patients infected with human immunodeficiency virus, dyslipidemia is frequently observed and characterized by elevated serum levels of triglycerides, reduced levels of total cholesterol, low-density lipoprotein and high-density lipoprotein-cholesterol with a predominance of small dense LDL particles [1,2]. Treatments with Protease inhibitors (PI) decrease HIV associated morbidity and mortality but lead to an increased risk of cardiovascular disease in part related to a strong increase of lipoprotein disturbances.…”

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The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART).We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5,2 H 3 ] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART.Subjects in group LD showed higher plasma triglycerides (5.73±3.58 vs 1.29±0.54 g/L, p<0.005), total cholesterol (2.98±0.95 vs 1.74±0.26 g/L, p<0.05), apoB (1.49±1.11 vs 0.51±0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7±42.2 vs 22.6±23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44±1.62 vs 1.60±0.61, p<0.05).

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“…We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5,2 H 3 ] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART.…”