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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A wide range of abnormalities of lipid metabolism have been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based highly active antiretroviral therapy, including hypertriglyceridaemia and hypercholesterolaemia. The increase of plasma lipid concentrations may involve up to 70-80% of HIV-positive subjects treated with a PI-containing regimen and are frequently (but not always) associated with the fat redistribution or the lipodystrophy syndrome. Multiple pathogenetic mechanisms by which antiretroviral agents lead to dyslipidaemia have been hypothesized, but they are still controversial. The potential clinicopathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations report an increased risk of premature coronary artery diseases in young HIV-positive individuals receiving PIs, besides peripheral atherosclerosis and acute pancreatitis. A limited-to-significant improvement of increased triglyceride and cholesterol plasma levels was described in patients who replaced PIs with nevirapine, efavirenz or abacavir, but the risks of long-term toxicity and virological relapse of this treatment switching are not completely defined. A hypolipidaemic diet and regular physical exercise may act favorably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or persists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance. Statins are considered the first-line therapy for the PI-related hypercholesterolaemia, while fibrates are the cornerstone of drug therapy when predominant hypertriglyceridaemia is of concern.
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PMID:Hyperlipidaemia in patients with HIV-1 infection receiving highly active antiretroviral therapy: epidemiology, pathogenesis, clinical course and management. 1292 47

Relatively little is known about the influence of dietary habits on the metabolic complications associated with human immunodeficiency virus (HIV) infection and lipodystrophy. Although recommendations to modify diet and exercise remain a first-line approach to the management of HIV-infected patients with dyslipidemia and glucose intolerance, it is important to determine to what extent, if any, these metabolic abnormalities may be attributed to or modified by dietary behaviors. I review previous work evaluating dietary behaviors and their relationship to lipid levels and insulin resistance in HIV-infected patients with and without lipodystrophy and discuss the implications of possible dietary interventions and results of preliminary studies of the effects of diet on dyslipidemia. Sound dietary guidelines based on investigational research among HIV-infected patients are clearly needed to help face the challenges of the emerging problems of hyperlipidemia, insulin resistance, and the possible increased risk of cardiovascular disease among patients with HIV infection and lipodystrophy.
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PMID:Dietary habits and their association with metabolic abnormalities in human immunodeficiency virus-related lipodystrophy. 1294 82

Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia, diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolic alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin, leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future.
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PMID:[Adverse effects of antiretroviral therapy. Aspects of pathogenesis]. 1456 6

Although the clinical application of HIV protease inhibitors (PIs) has markedly reduced HIV-related morbidity and mortality, it is now recognized that PI-based therapy often causes serious metabolic disorders, including hyperlipidemia and premature atherosclerosis. The etiology of these adverse effects remains obscure. Here, we demonstrate that deficiency of the fat-derived hormone adiponectin might play a role. The steady-state mRNA levels of the adiponectin gene and secretion of this protein from 3T3-L1 adipocytes are significantly decreased after treatment with several PIs (indinavir, nelfinavir, and ritonavir), with ritonavir having the greatest effect. Intragastric administration of ritonavir into mice decreases plasma concentrations of adiponectin and concurrently increases the plasma levels of triglyceride, free fatty acids, and cholesterol. Adiponectin replacement therapy markedly ameliorates ritonavir-induced elevations of triglyceride and free fatty acids. These beneficial effects of adiponectin are partly due to its ability to decrease ritonavir-induced synthesis of fatty acids and triglyceride, and to increase fatty acid combustion in the liver tissue. In contrast, adiponectin has little effect on ritonavir-induced hypercholesterolemia and hepatic cholesterol synthesis. These results suggest that hypoadiponectinemia is partly responsible for the metabolic disorders induced by HIV PIs, and adiponectin or its agonists might be useful for the treatment of these disorders.
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PMID:Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice. 1473 52

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.
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PMID:Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy. 1495 94

The introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has transformed HIV/AIDS into a chronic illness and the focus of clinical management has shifted from opportunistic infections to long-term management and toxicities of therapy. Pediatric patients with HIV infection perhaps pose the greatest challenge in this arena as they potentially face many decades of living with HIV/AIDS and its therapies. Although there are numerous emerging medical complications associated with chronic HIV infection and HAART, hyperlipidemia is increasingly recognized among HIV-infected children and adults and will be the focus of this review. The nature and prevalence of lipid abnormalities in children with HIV infection is discussed, as well as possible etiologies for these abnormalities and the future management of this growing challenge for children living with HIV disease.
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PMID:Hyperlipidemia in children with HIV infection: an emerging problem. 1503 Mar 4

In this review we summarise the data on the effects of HIV infection and its therapy with antiretroviral drugs on adhesion molecules, considered to be potential biomarkers of endothelial cell function. This is a recent area of interest, given the unexpected associations between antiretroviral therapy, metabolic alterations of lipid profile, and the risk of cardiovascular disease in the absence of clear pathogenetic links. Although convincing prospective data are still scarce, it seems timely to elucidate the potential value of non-invasive, inexpensive tests for predicting cardiovascular risk in HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Endothelial function, the most plausible link between infection, inflammation, and atherosclerosis, has been investigated since the beginning of the HIV epidemic. Increased concentrations of soluble adhesion molecules, such as those from the selectin and immunoglobulin families, have consistently been reported in HIV-positive patients. The introduction of HAART has renewed interest in the study of endothelial function in HIV-positive patients, in view of some HAART-related metabolic abnormalities (hyperlipidaemia, hyperglycaemia, fat redistribution) and several large reports of premature coronary artery disease. Whether HAART reduces endothelial injury associated with HIV infection or contributes to further endothelial cell activation is still a matter of controversy. Also unclear is whether HAART acts directly or indirectly, and if protease inhibitors and other classes of antiretroviral drugs differ in their proatherosclerotic effects. This article attempts to define the state of these emerging issues, identifies areas of controversy and of potential clinical relevance, and suggests some directions for future research.
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PMID:HIV infection, HAART, and endothelial adhesion molecules: current perspectives. 1505 Sep 39

A wide range of morphologic alterations and lipid metabolism abnormalities have been recently described in HIV-infected patients receiving a protease inhibitor-based highly active antiretroviral therapy. The hyperlipidaemia may involve up to 70-80% of HIV-positive subjects treated with a protease inhibitor-containing regimen, and it is frequently (but not always) associated with the fat redistribution syndrome or lipodystrophy. The potential clinico-pathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations reported an increased risk of prematury coronary artery diseases in young HIV-positive individuals receiving protease inhibitors, besides peripheral atherosclerosis and acute pancreatitis. A hypolipidaemic diet and regular physical exercise may act favourably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or pesists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance.
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PMID:[Lipodystrophy and lipid metabolism alterations in HIV-infected patients receiving highly active antiretroviral therapy (HAART)]. 1520 80

Body fat changes and metabolic abnormalities such as hyperlipidaemia and diabetes have been increasingly reported following the successful introduction of highly active antiretroviral therapy (HAART). These side effects were attributed initially to the use of protease inhibitors (PIs). As a consequence, a series of trials were conducted where patients with well-controlled HIV viraemia either continued on PIs or were switched to a simplified maintenance therapy (SMT) without PIs. Evidence from these trials is still insufficient to show that switching from PIs to either abacavir, nevirapine or efavirenz is safe. However, patients with suboptimal pre-HAART treatment are at increased risk of virological failure if switched to an SMT. Patients switched from PI regimens tend to stay longer on an SMT and those switched to abacavir show a reduction in total cholesterol, but there is no evidence of any additional benefit from non-PI-based SMT. There is a clear need for a better understanding of HAART-related lipodystrophy and metabolic toxicity, and pharmacogenetic tests to identify those patients most at risk. The advent of simpler formulations for all drug classes, and new PIs with less metabolic toxicity, is likely to reshape completely the role of SMT.
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PMID:Protease inhibitor-sparing simplified maintenance therapy: a need for perspective. 1526


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