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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As new therapies for HIV infection have been developed, some of the clinical focus related to AIDS and HIV infection has shifted from acute care, to more chronic issues. Some of these new clinical issues seem related to the HIV infection itself, while others seem to be side effects of therapeutic efforts. Metabolic abnormalities, such as dyslipidemia, insulin resistance, and lipodystrophy (LD) have been observed. The clinical importance of these is demonstrated by the increased prevalence of cardiovascular disease and diabetes in HIV infected persons. LD is a general term used to describe varying degrees of fat redistribution, including lipoatrophy and lipohypertrophy, in different body regions. Though LD was observed in persons with HIV infection before highly active treatment regimens were developed, the prevalence of LD has seemingly increased drastically with the widespread use of more active therapies. It has been postulated that protease inhibitors (PI), especially, are linked to the development of LD. This review will assess the epidemiologic information related to HIV-associated LD, and related metabolic syndromes. In addition, potential mechanisms accounting for these syndromes will be reviewed. In general, the available data do not define a single, definable etiology or mechanism explaining these clinical conditions, but suggest that these conditions are caused by a complex interaction potentially involving such things as the side effects of medications, alteration of immune function, and individual subject characteristics, such as body weight and baseline lipid level.
Atherosclerosis 2004 May
PMID:HIV-related lipodystrophy and related factors. 1513 44

chlamdAs with other organ systems, the vulnerability of the nervous system to infectious agents increases with aging. Several different infectious agents can cause neurodegenerative conditions, with prominent examples being human immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of the central nervous system (CNS) typically have a relatively long incubation period and a chronic progressive course, and are therefore increasing in frequency as more people live longer. Infectious agents may enter the central nervous system in infected migratory macrophages, by transcytosis across blood-brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses and lipid rafts are important sites at which infectious agents may enter neurons and/or exert their cytotoxic effects. Recent findings suggest the possibility that infectious agents may increase the risk of common age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and influenza promote damage to neurons during aging, there is no conclusive evidence for a major role of these pathogens in neurodegenerative disorders. In the case of stroke, blood vessels may be adversely affected by bacteria or viruses resulting in atherosclerosis.
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PMID:Infectious agents and age-related neurodegenerative disorders. 1516 5

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

HIV infection is associated with disturbances in lipid metabolism due to a host's response mechanism and the current antiretroviral therapy. The pathological appearance and progression of atherosclerosis is dependent on the presence of injurious agents in the vascular endothelium and variations in different subsets of candidate genes. Therefore, the Hha I polymorphism in the apolipoprotein E gene was evaluated in addition to triglycerides, total cholesterol, very low-density lipoprotein (VLDL), LDL, high-density lipoprotein (HDL), and apolipoprotein (apo) Al, B and E levels in 86 Brazilian HIV-infected patients and 29 healthy controls. The allele frequency for apoE in the HIV-infected group and controls was in agreement with data on the Brazilian population. Dyslipidemia was observed in the HIV group and verified by increased levels of triglycerides, VLDL and apoE, and decreased levels of HDL and apoAl. The greatest abnormalities in these biochemical variables were shown in the HIV-infected individuals whose immune function was more compromised. The effect of the genetic variation at the APOE gene on biochemical variables was more pronounced in the HIV-infected individuals who carried the apoE2/3 genotype. The highly active anti-retroviral therapy (HAART)-receiving group presented increased levels of total cholesterol and apoE. Dyslipidemia was a predictable consequence of HIV infection and the protease inhibitors intensified the increase in apoE values.
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PMID:Abnormalities in apolipoprotein and lipid levels in an HIV-infected Brazilian population under different treatment profiles: the relevance of apolipoprotein E genotypes and immunological status. 1520 89

HIV-1-infected patients exhibit severe damages of the aortic endothelium, develop angioproliferative lesions such as Kaposi's sarcoma (KS), and have an increased risk of cardiovascular diseases and atherosclerosis. An increased adhesion of leukocytes to the endothelium is a common pathogenic parameter of AIDS-associated vascular diseases. Here we show that the HIV-1 Tat protein, a regulatory protein of HIV-1 released by infected cells, and TNF-alpha, a cytokine increased in sera and tissues of HIV-1-infected patients, activate synergistically the adhesion of leukocytes to endothelial cells both in vitro and in vivo. This effect is selectively mediated by HIV-1 Tat, since HIV-1 Nef, another HIV-1 regulatory protein, and the HIV-1 envelope protein gp41, had no effect. In vitro adhesion assays with PBMC and quantitative cell type analysis of adherent cells by FACS demonstrated that HIV-1 Tat selectively activates the adhesion of T-cells and monocytes but not of B-cells. Intravital microscopic studies in mice confirmed the synergistic activity of HIV-1 Tat and TNF-alpha on leukocyte adhesion to the endothelium in vivo. These data indicate that HIV-1 Tat in cooperation with TNF-alpha may contribute to the vascular damage and cardiovascular diseases observed in AIDS patients but also to the prominent extravasation of T-cells and monocytes which is a key process in the formation and progression of KS lesions.
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PMID:HIV-1 Tat increases the adhesion of monocytes and T-cells to the endothelium in vitro and in vivo: implications for AIDS-associated vasculopathy. 1524 52

HIV infection is a global public health issue that is frequently associated with cardiovascular involvement. These HIV-associated cardiovascular manifestations are often clinically occult or attributed incorrectly to other non-cardiac disease processes. A heightened awareness and routine screening for cardiovascular involvement in HIV-infected patients leads to earlier detection and the hope for a reduction in associated morbidity and mortality. Left ventricular dysfunction, an independent predictor of mortality in HIV-infected patients, is the result of many causes in this population and may result in dilated cardiomyopathy and congestive heart failure in about 10% of patients. Other HIV-associated cardiovascular problems include infective endocarditis, cardiovascular malignancy, pulmonary arterial hypertension, vasculitis, pericardial effusion, premature atherosclerosis, and arrhythmias. HIV-associated cardiovascular emergencies include congestive heart failure, pulmonary edema, supraventricular and ventricular arrhythmias, endocarditis, and tamponade. Anti-infective and immunomodulatory therapies may be particularly helpful in this population to reduce associated cardiovascular disease. Highly active antiretroviral therapy may result in lipodystrophy, hyperlipidemia, truncal adiposity, and insulin resistance that can be improved by physical activity and training programs. Cardiovascular complications of therapeutic drugs in HIV-infected patients include torsade de pointes, congestive heart failure, dyslipidemia, accelerated atherosclerosis, and myocardial infarction. In summary, cardiovascular complications are important contributors to morbidity and mortality in HIV-infected patients that can be detected early in many cases and treated effectively.
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PMID:HIV-related cardiovascular disease and drug interactions. 1544 73

Endothelial dysfunction is a critical initial step of atherogenesis that subsequently contributes to the progression and clinical manifestations of atherosclerosis. The use of human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) agents has been associated with increased cardiovascular events and worsening of multiple coronary heart disease risk factors including dys-lipidemia, insulin resistance, and endothelial dysfunction. Endothelial dysfunction may be caused by HIV infection itself as well as treatment-related effects of the antiretroviral agents used to treat HIV. The available evidence suggests that PIs may induce endothelial dysfunction via their effects on both lipid and glucose metabolism. Studies in healthy subjects confirm a role for reduced endothelial nitric oxide production in the endothelial dysfunction associated with the PI indinavir. Further work is needed to determine the relative tendencies of other antiretroviral agents to induce endothelial dysfunction, the physiologic mechanisms involved, and the contribution of the metabolic and body shape changes associated with HIV treatment-related lipodystrophy, and to establish effective interventions for endothelial dysfunction in HIV-infected patients.
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PMID:Clinical aspects of endothelial dysfunction associated with human immunodeficiency virus infection and antiretroviral agents. 1547 Feb 73

The heart is frequently affected in patients with the acquired immune deficiency syndrome (AIDS). Although the introduction of potent antiretroviral therapy (ART) has produced a sharp decline in mortality and morbidity in HIV-infected patients, the use of ART is associated with the development of peripheral insulin resistance, dyslipidemia, and lipodystrophy. These abnormalities are also associated with coronary artery disease, and numerous reports of myo-cardial infarction in young HIV-infected patients have raised concerns of pre-mature coronary disease in this population. A comprehensive review of the epidemiology of coronary artery disease is given. In recent years, several non-invasive methods to detect early development of atherosclerosis have been evaluated. Two noninvasive techniques using ultrasound have emerged as valid methods to detect early development of atherosclerosis: intima-media thickness and endothelial dysfunction assessed by the measurement of flow-mediated brachial artery dilatation. Multicenter, randomized trials using either technique may provide more information about whether HIV infection alone, long-term HAART use, or both may increase the risks of or accelerate coronary disease in HIV-infected patients.
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PMID:Cardiovascular effects of antiretroviral therapy and noninvasive assessments of cardiovascular disease in HIV infection. 1547 Feb 75

Highly active antiretroviral therapy (HAART) has significantly improved the prognosis of HIV-1-infected patients but is associated with significant side effects such as diabetes, atherosclerosis, and cardiovascular complications. Oxidative stress can disrupt endothelial homeostasis by dysregulating the balance between pro- and antiatherogenic factors. We hypothesized that chronic exposure to HAART results in endothelial oxidative stress and activation of mononuclear cell recruitment, an early event in atherosclerosis. We studied the effects of HAART drug combinations, consisting of zidovudine, a nucleoside reverse transcriptase inhibitor; efavirenz, a nonnucleoside reverse transcriptase inhibitor; and either of the two protease inhibitors (PIs), indinavir or nelfinavir, on human aortic endothelial cells (HAECs) by monitoring the following parameters: (1) generation of reactive oxygen species (ROS), (2) mono-nuclear cell (Jurkat or U-937) adhesion, and (3) expression of cell adhesion molecules (CAMs). HAART exposure increased ROS formation in HAECs. Exposure to PIs alone and in HAART combinations increased mononuclear cell adhesion to HAECs in a concentration-dependent manner. Mononuclear cell adhesion to HAART-exposed HAECs was significantly enhanced following acute (24-h) exposure to the inflammatory cytokines, tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta and was suppressed by the antioxidants N-ace-tylcysteine and glutathione. Exposure to HAART increased intercellular adhesion molecule-1 (ICAM-1) gene expression and concomitant exposure to TNF-alpha further increased ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule cell surface protein levels. These studies indicate that chronic HAART exposure increases oxidative stress in endothelial cells and induces mononuclear cell recruitment, which may eventually precipitate the cardiovascular diseases observed in HIV-1+ individuals on antiretroviral therapy.
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PMID:HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells: exacerbation by inflammatory cytokines and amelioration by antioxidants. 1547 Feb 76

Current antiretroviral therapy protocols enable long-term survival of HIV-infected patients, decreasing the risk of infectious complications. Three classes of anti-HIV treatments are available. With longer survival, unusual cardiovascular complications related to iatrogenic biological anomalies (dyslipidemia and impaired glucose tolerance) have appeared among this young population which is exposed to usual risk factors of atherosclerosis. Antiretroviral therapies are suspected to cause these complications, inducing maturity-onset diabetes in 4 to 20% of patients, impaired glucose tolerance in 15 to 60%, hypertriglyceridemia in 15 to 74% depending on the survey, and hypercholesterolemia in 20 to 60%, especially in case of associated lipodystrophia. A lipid battery including total cholesterol, HDL, and triglycerides, and 12-h fasting blood glucose should be obtained before initiating antiretroviral therapy. Any anomalous finding should be followed carefully with regular surveillance every 3 to 6 months and search for other causes of secondary dyslipidemia. In the event of casual and persisting elevation of LDL-cholesterol levels, a statin treatment can be introduced. For secondary prevention, irrespective of the context, recommendations currently merge with the consensus applying to the general population. These patients require careful surveillance of cardiovascular risk factors and a specific care in addition to treatment of their immunodeficiency.
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PMID:[Antiretroviral therapy and cardiovascular risk]. 1552 82


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