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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly active antiretroviral therapy has dramatically improved the quality of life and life expectancy of patients with human immunodeficiency virus. However, the prolonged use of HAART leads to severe metabolic adverse events. Both HIV infection and HAART can cause changes in lipid and glucose metabolism as well as elevation of blood pressure, promoting the development of atherosclerosis. Cardiovascular diseases have become a major cause of mortality among HIV-infected subjects who respond well to antiretroviral therapy. Nevertheless, a proper lifestyle and pharmacologic intervention can improve cardiovascular risk factors in the HIV-treated population and significantly reduce healthcare investments in the treatment of future cardiovascular complications in this population. In this review we summarize the current knowledge of CVD prevention and treatment in HIV patients.
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PMID:Cardiovascular disease prevention and treatment in patients with human immunodeficiency virus. 1584 7

Human immunodeficiency virus (HIV) protease inhibitors have been successfully used in highly active antiretroviral therapy for HIV-1 infection. Treatment of patients infected with HIV with HIV protease inhibitors is unfortunately associated with a number of clinically significant metabolic abnormalities and an increased risk of premature atherosclerosis and myocardial infarction. However, the cellular/molecular mechanisms of the HIV protease inhibitor-induced lipid dysregulation and atherosclerosis remain elusive. Macrophages are the most prominent cell type present in atherosclerotic lesions and play essential roles in both early lesion development and late lesion complications. In this study, we demonstrate that three different HIV protease inhibitors (ritonavir, indinavir, and atazanavir) induce endoplasmic reticulum stress and activate the unfolded protein response in mouse macrophages. Furthermore, at therapeutic concentrations (5-15 microM), these HIV protease inhibitors were found to increase the levels of transcriptionally active sterol regulatory element binding proteins, decrease endogenous cholesterol esterification, cause the accumulation of free cholesterol in intracellular membranes, deplete endoplasmic reticulum calcium stores, activate caspase-12, and increase apoptosis in macrophages. These findings provide possible cellular mechanisms by which HIV protease inhibitors promote atherosclerosis and cardiovascular disease in HIV-1 infected patients treated with HIV protease inhibitors.
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PMID:HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease. 1597 36

Highly active antiretroviral therapy (HAART) has greatly extended the lives of people infected with the human immunodeficiency virus (HIV). This reduced risk of early death from opportunistic infections or other sequelae of HIV infection, however, means that other possible causes of death emerge. Myocardial infarction has become a matter of particular concern. Two of the main sources of cardiovascular disease in this population are believed to be vascular inflammation and dyslipidemia. We review the evidence for this hypothesis and discuss the relationship of HIV to vascular inflammation. Current treatment guidelines do not recommend the immediate initiation of HAART unless warranted, potentially allowing long-term, unchecked viral impact on the development of atherosclerosis. Finally, we consider the protease inhibitors traditionally included in HAART regimens and their relationship to the development of dyslipidemia, as well as other classes of antiretrovirals, such as the non-nucleoside reverse transcriptase inhibitors, which might be a better choice for patients with cardiovascular risks. Other strategies, such as pharmacologic, nutritional, and physical activity interventions are discussed. The patients who might benefit most are those in whom the precursors of vascular plaques, such as fatty streak, smooth muscle cell, macrophage, and T-lymphocyte aggregation not yet identified by echocardiographic and biopsy findings have already developed as a result of unchecked viral inflammation and replication.
Atherosclerosis 2006 Mar
PMID:Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis. 1629 90

As part of highly active antiretroviral therapy, protease inhibitor treatment has significantly increased the lifespan of human immunodeficiency virus (HIV)-infected individuals. Many patients, however, develop negative side effects, including premature atherosclerosis. We have previously demonstrated that in male low density lipoprotein receptor (LDL-R) null mice, HIV protease inhibitors induce atherosclerotic lesions and cholesterol accumulation in macrophages in the absence of changes in plasma lipid levels. We determined that these increases were due to an up-regulation of the scavenger receptor, CD36. In the present study, we examined the effects of HIV protease inhibitors in female LDL-R null mice. Female mice given ritonavir and amprenavir (23 and 10 microg/mouse/day, respectively) developed fewer atherosclerotic lesions than males. Furthermore, peritoneal macrophages isolated from ritonavir-treated females had reduced levels of cholesterol accumulation as compared with males, and CD36 protein levels were increased to a significantly lesser degree in females than in males. To investigate the molecular mechanisms of this gender difference, we examined the effect of genetically removing estrogen receptor-alpha (ERalpha). In female mice lacking both LDL-R and ERalpha, the protective effect of gender was lost. Additionally, the reduced levels of cholesterol accumulation in macrophages observed in females was reversed. Furthermore, the absence of ERalpha resulted in increased expression of CD36 protein in a macrophage-specific manner in mice treated with ritonavir. These data demonstrate that ERalpha is directly involved in the regulation of cholesterol metabolism in macrophages and plays an important role in the gender differences observed in HIV protease inhibitor-induced atherosclerosis.
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PMID:Estrogen receptor-alpha mediates gender differences in atherosclerosis induced by HIV protease inhibitors. 1629 1

Infections have long been recognized as a potential, if uncommon, cause of cerebrovascular disease. In recent years, with the growing recognition of the importance of inflammation in atherosclerosis, there has been renewed interest in the possibility that common infections may participate in the atherosclerotic process or lead to stroke through other mechanisms. Specific organisms that have been implicated include Chlamydia pneumoniae, herpes viruses, human immunodeficiency virus, Helicobacter pylori, and organisms associated with periodontal infections. This article outlines the epidemiological, pathological, and laboratory evidence that these infections may be associated with atherosclerosis and stroke. Although definitive proof of an association between a specific infection and stroke is generally lacking, the accumulating evidence does indicate that several types of infections may be among the modifiable risk factors that contribute to the risk of stroke.
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PMID:Do common infections cause stroke? 1647 47

Toll-like receptors (TLRs) play an important role in innate immunity. Individual TLRs recognise microbial components that are conserved among pathogens. Such recognition initiates necessary inflammatory immune responses and induces subsequent activation of adaptive immunity. Studies in people with polymorphisms in genes encoding TLR signalling can elucidate the relationship between TLRs and human diseases, such as infectious diseases, atherosclerosis and immunodeficiency. Indeed, accumulating data in respect to TLR signalling suggest that TLRs are closely related with the pathogenesis of autoimmune diseases. This review looks at the role of TLRs in various immune disorders, and discusses the pathogenesis of diseases.
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PMID:The role of Toll-like receptors in immune disorders. 1650 31

The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM), initiated in 2000, investigates the prevalence and correlates of changes in fat distribution, insulin resistance, and dyslipidemia among human immunodeficiency virus (HIV)-infected men and women compared with a population-based group of control men and women. Between June 2000 and September 2002, 1,480 participants (1,183 HIV-infected persons and 297 controls) were enrolled in FRAM. Measurements taken included whole-body magnetic resonance imaging for quantification of regional fat, anthropometric measurements, central laboratory analysis of metabolites, and assessment of symptoms, sociodemographic factors, and lifestyle. Similar measurements were repeated among FRAM participants 4 years later (FRAM 2) for investigation of the progression of fat distribution changes, insulin resistance, and hyperlipidemia. In FRAM 2, which is ongoing, investigators are also determining the associations of subclinical cardiovascular disease, as measured by carotid intimal-medial wall thickness, with HIV infection, fat distribution changes, insulin resistance, and other proatherogenic changes in serum lipid levels. The demographic characteristics of HIV-infected FRAM men and women were comparable to those reported from a national random sampling of HIV-infected men and women receiving medical care in the United States. The representativeness of the FRAM sample increases its value as a resource for studies on fat distribution, metabolic changes, and atherosclerosis in HIV infection.
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PMID:The study of fat redistribution and metabolic change in HIV infection (FRAM): methods, design, and sample characteristics. 1652 55

Atherosclerosis obliterance and critical lower limb ischemia lead to immunodeficiency and disbalance of T- and B- components of immune system. Surgical treatment doesn't eliminate but in a number of cases aggravates immune disorders. Immunocorrection stimulates anti-infectious protection. Indications to different variants of immunocorrection are formulated.
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PMID:[Immunological disorders and correction of them in surgical patients with atherosclerosis obliterance]. 1688 38

Several types of cardiovascular lesions may develop in pediatric human immunodeficiency virus-positive (HIV+)/acquired immunodeficiency syndrome (AIDS) patients, namely myocarditis, dilated cardiomyopathy, pericardial effusion, pericarditis, left ventricle hypertrophy, fibrocalcific arteriopathy, and aneurysms. Additional lesions may be discovered by histological examination. These include fibrocalcific lesions in medium-sized arteries and small vessels, mainly of the heart and brain, and vasculitis. In the large arteries the vasa vasorum may present chronic inflammatory infiltrates or leukocytoclastic vasculitis, resulting in aneurysms. We are reporting the case of a 14-year-old girl with mother-to-infant HIV transmission with a long history of several central nervous system infections and AIDS dementia, who received treatment with the HAART protocol (including a protease inhibitor) for 3 years. A year after beginning this treatment, cholesterol serum levels were 2.8 g/L and 3.8 g/L. Autopsy findings showed gross and microscopic features of adult-type atherosclerosis involving the whole thoracic aorta, its main branches, and the coronary arteries. Remarkably, the abdominal aorta and all its branches were almost completely devoid of these lesions. At the same time, although the body presented extreme cachexia, there were obvious subepericardial, periadrenal, and peripancreatic fat deposits. The referred findings may have resulted from the well-known metabolic-dyslipemic syndrome induced by the HAART therapy and have not been specifically mentioned previously in the literature in the particular setting observed in the case of this patient.
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PMID:Atherosclerosis and central adiposity in a pediatric patient with AIDS treated with HAART: autopsy findings. 1716 94

As we have become more familiar with the pathogenesis of atheroma, it has become recognized atherogenesis is mainly an inflammatory disease. Therefore, it is not surprising that a body of evidence demonstrates that endothelium injury is associated with the progression and severity of HIV infection. Another important question is: do antiretroviral drugs increase or reduce endothelial injury? Various studies support the hypothesis that HAART does induce activation of endothelial function. Thus, HIV virus as well as immune reconstitution and HAART itself promote premature endothelial activation. Such a prominent role played by inflammatory events could affect the structure of the arterial lesions in HIV patients that could present different characteristics with respect to the classical atheroma. In fact, in two HIV patients with severe stenosis of the carotid, histology revealed extensive inflammatory infiltration of the vascular wall. The characteristics of these lesions were similar to those of arteritis. Another study evidenced that the ultrasonographic structure of the lesions in HIV patients substantially differ from those found in atherosclerosis, sharing similar characteristics with arteritis. We hypothesize that the atherosclerotic lesions in HIV patients develop in two distinct phases: the first one characterized by an inflammation of the vascular wall, and subsequently, the lesions could evolve towards the classic feature of the atheroma. The lesions in the first phase are probably determined by immunodeficiency, immune reconstitution, and the same effect of HAART. In the second phase they could be maintained by the classic risk factors.
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PMID:Atherosclerosis in HIV patients: a new face for an old disease? 1721 35


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