Abstract and Introduction
Abstract
Background: Alterations in serum lipids and an increased risk of myocardial infarction have been associated with HIV-1 infection and its treatment.
Methods: Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy in frozen plasma samples from participants in the Multicenter AIDS Cohort Study. The effects of HIV-1 infection, antiretroviral therapy, and other factors on median particle concentrations were examined using quantile regression.
Results: Fasted samples were tested from 1082 men, including 609 HIV-seronegative and 473 HIV-1-infected men. Compared with HIV-seronegative men, HIV-1-infected men on antiretroviral therapy had an atherogenic phenotype with higher numbers of very low density lipoprotein and small low-density lipoprotein particles and lower numbers of high-density lipoprotein and large low-density lipoprotein particles. HIV-infected, antiretroviral-naive men had significantly lower high-density lipoprotein and small low-density lipoprotein particle concentrations compared with the HIV-seronegative men. Among men on antiretroviral therapy, the atherogenic phenotype was most pronounced in men with a good clinical status.
Conclusion: Use of antiretroviral therapy in HIV-1-infected men was associated with an "atherogenic lipoprotein phenotype."
Introduction
Abnormalities in serum lipid concentrations have been associated with both HIV-1 infection itself and its treatment with highly active antiretroviral therapy (HAART). In addition to lipid changes, HAART may result in metabolic disturbances such as insulin resistance, peripheral lipoatrophy, and central adiposity. Large prospective observational studies have suggested that use of HAART, particularly HIV-1 protease inhibitors (PIs), was associated with an increased risk of myocardial infarction that is partially mediated by serum lipid abnormalities.
Nuclear magnetic resonance (NMR) spectroscopy can be utilized to quantify the number of particles of specific lipoprotein subclasses. Numerous studies have evaluated the relationship of lipoprotein subclasses and future cardiovascular events. Although not conclusive, the data suggest that smaller low-density lipoprotein (LDL) particle size, specifically a predominance of small dense LDL or a greater number of small LDL particles (LDL-p), is a predictor of coronary disease. Insulin resistance and hypertriglyceridemia are associated with a decrease in average LDL size, due to both an increase in the concentration of small LDL-p and a decrease in large LDL-p.
Austin described an "atherogenic lipoprotein phenotype" (ALP) based on a predominance of small, dense LDL-p with accompanying elevated triglycerides and reduced high-density lipoprotein cholesterol (HDL-C). Obesity, diabetes, and insulin resistance are known to be associated with elevated triglycerides and reduced HDL-C, and by NMR, this pattern has been shown to be associated with substantially increased numbers of small LDL-p and decreased numbers of large LDL-p. In this paper, we will use ALP to describe a pattern of elevated triglycerides, reduced HDL-C, elevated small LDL-p, and reduced large LDL-p, which has been given increased emphasis in recently published guidelines of the National Cholesterol Education Program and which we observed with some consistency in the results presented here.
The objective of this study was to describe the distribution of selected lipoprotein subclasses among participants in the Multicenter AIDS Cohort Study (MACS), including HIV-seronegative men, HIV-infected men not on HAART, and HIV-infected men on HAART. The factors that predict alterations in the lipoprotein subclasses were assessed. In HIV-infected individuals treated with antiretroviral medications, differences in serum lipids have been observed between and within drug classes. We hypothesized that PI-containing regimens would have a more atherogenic profile [more total very low density lipoprotein particles (VLDL-p) and small LDL-p] than nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Within the PI class, we predicted that ritonavir-containing regimens would have the highest total VLDL-p concentration and that atazanavir-containing regimens would have a less atherogenic profile compared with other PI regimens.