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

The use of highly active anti-retroviral therapy (HAART) is associated with long-term adverse metabolic events including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of the present study was to prospectively examine the mechanism of HAART-induced hyperlipidemia in HIV-seropositive, HAART-naive men prior to the development of frank lipodystrophy. Patient's (n = 13) weight, BMI, lean mass, and percent fat mass, waist circumference did not change after 8 weeks of treatment with HAART. Plasma FFA concentration was already elevated in HAART-naive patients compared to healthy, untreated, HIV negative control individuals and was further increased after 8 weeks of HAART in the former. Insulin-mediated suppression of plasma FFA concentrations was impaired both prior to and following introduction of HAART, compared to healthy, matched controls. VLDL-apoB and VLDL-TG concentrations rose significantly from normal levels after HAART. Compared to healthy control subjects, VLDL fractional catabolic rate and clearance in HIV-seropositive individuals was reduced by approximately 40%, a defect that was not corrected after HAART. The increase in VLDL after HAART was explained by an increase of VLDL-apoB and VLDL-TG secretion towards normal while the impaired VLDL clearance remained unchanged. We conclude that elevation of circulating VLDL early in the course of HAART is caused by the combination of impaired VLDL clearance already present in HAART-naive HIV-seropositive patients and HAART-mediated increase in VLDL secretion. These changes occur concomitantly with an elevation of plasma free fatty acids but before significant change in body composition.
Atherosclerosis 2005 Jan
PMID:Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals. 1558 14

A 32-year-old woman presented with a painful leg and a gangrenous big toe. Her medical history included HIV-infection that had remained untreated for 8 years. In addition, she had smoked about 10 cannabis-cigarettes daily during the previous 15 years. Physical examination and angiography confirmed the presence of severe peripheral artery disease in the left lower leg. She received a femorodistal bypass graft but the gangrene was progressive, ultimately necessitating a lower leg amputation. Histopathological examination revealed intimal fibrosis and thrombosis with recanalisation in combination with fragmentation of the internal elastic membrane. Peripheral artery disease is often associated with lower extremity ischaemia, mostly affecting elderly patients and almost always caused by atherosclerosis. When ischaemic symptoms manifest themselves in young individuals (<40 years), rare causes of obliterative arterial disease, such as inflammation or post-traumatic vascular injury, must be excluded. Use of cannabis and untreated HIV infection are both relatively unknown risk factors for the onset of premature non-atherosclerotic arterial disease. Stopping the smoking of cannabis appears to have a favourable effect on the ischaemic symptoms. Whether treatment of HIV-infection can affect the course of premature peripheral vascular disease is unknown. When deciding whether or not to give antiviral therapy, care providers should also consider the increased cardiovascular mortality rates associated with these treatment regimens. In the case described, the HIV-infection was considered the most likely cause of the peripheral artery disease, based on all the histopathological findings.
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PMID:[Cannabis use and untreated HIV-infection: unknown risk factors for premature peripheral artery disease]. 1561 77

Accumulating clinical evidence now links HIV protease inhibitors (HPIs) to the pathogenesis of insulin resistance, dyslipidaemia, lipodystrophy and atherosclerosis associated with highly active anti-retroviral therapy. Here we briefly describe the evidence for a distinct causative role for HPIs, and explore the cellular mechanisms proposed to underlie these side-effects. Acute inhibition of GLUT4-mediated glucose transport, and defective insulin signalling induced by chronic exposure to nelfinavir, are described as cellular mechanisms of insulin resistance. Interference with adipogenesis and adipocyte apoptosis and nelfinavir-induced activation of lipolysis are discussed as potential mechanisms of HPI-induced lipodystrophy. HPI-induced free radical production, apoptosis and increased glucose utilization in vascular smooth muscle cells are presented as possible novel mechanisms for atherosclerosis. Common pathways and cause-effect relationships between the various cellular mechanisms presented are then discussed, with emphasis on the role of insulin resistance, free radical production and enhanced lipolysis. Understanding the cellular mechanisms of HPI-induced side-effects will enhance the search for improved anti-retroviral therapy, and may also shed light on the pathogenesis of common forms of insulin resistance, dyslipidaemia and atherosclerosis.
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PMID:Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors. 1565 21

We report a successful case of a conventional coronary artery bypass operation performed in a patient with HIV infection and severe three-vessel coronary artery disease. The signal change in outcome of HIV disease, in addition to the reported evidence for accelerated atherosclerosis caused by the disease itself and by its treatment with protease inhibitors, is likely to produce a larger population of HIV-infected patients developing premature coronary artery disease for whom cardiac surgery will be required. Surgical risk, outcome and operative team risk are discussed.
HIV Med 2005 Jan
PMID:Coronary artery bypass grafting in a patient with HIV. 1567 Feb 53

It is widely accepted that vascular mechanisms are involved in the genesis of many neurological disorders. In particular, blood-brain barrier (BBB) dysfunction has been related to the severity of Alzheimer's disease, encephalopathy due to meningitis, multiple sclerosis, HIV-associated encephalopathy, epilepsy, gliomas and metastatic brain tumors. The BBB may constitute an important therapeutic target to protect neurons after CNS diseases. Both in vivo and in vitro, the functional phenotype of vascular endothelium is dynamically responsive to circulating cytokines, growth factors and puslatile blood flow (shear stress). Shear stress can play a critical role in vascular homeostasis and pathophysiology; it is a major regulator of remodeling in developed blood vessels and in blood vessels affected by atherosclerotic lesions. The physiological fluid mechanic stimulus, shear stress, could be considered to be an important 'differentiative' stimulus capable of modulating endothelial phenotype in vivo. Endothelial cells undergo cell cycle arrest after exposure to physiological levels of shear stress. As for mature endothelial cells, in which flow mediated shear stress may play a role in the induction, progression and/or prevention of atherosclerosis by changing their function, stress may play a role in endothelial cell differentiation from hemopoietic stem cells and/or from embryonic stem cells. Stem cells may be used to repair vascular damage, including loss of EC, due to a variety of diseases (e.g. myocardial neovascularization by adult bone marrow derived angioblasts). In the brain, it was proposed that neuron-producing stem cells may be used to treat Alzheimer's disease, paralysis, etc. Surprisingly, very few investigators are exploring the use of endothelial precursors to revert or prevent cerebrovascular disease. This review summarizes the most recent data related to cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in blood-brain barrier homeostasis and pathophysiology.
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PMID:The cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in vascular homeostatis and pathophysiology. 1572 68

Prolonged treatments with inhibitors of human immunodeficiency(HIV)-encoded protease (ARPI) have been reported to induce early atherosclerotic events. Our in vitro study indicates that alpha-tocopherol may prevent drug-induced premature atherosclerosis since it interferes with CD36 scavenger receptor over-expression induced by ritonavir in monocytes. The mechanism of CD36 upregulation by ritonavir involves inhibition of the ubiquitin-proteasome system and alpha-tocopherol is able to normalize proteasome activity. These findings suggest that ARPI combined with early alpha-tocopherol supplementation may decrease the drug-induced atherosclerotic risk.
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PMID:HIV protease inhibitors-induced atherosclerosis: prevention by alpha-tocopherol. 1581 62

This study reported the changes in carotid intima-media thickness (IMT) during a 36-month period in 233 HIV-infected patients. Median IMT increased in the first 12 months and then decreased by month 36. The prevalence of treatment with lipid-lowering agents and protease inhibitor-free highly active antiretroviral therapy regimens increased, whereas smoking prevalence decreased. The progression of atherosclerosis in HIV-infected patients can be controlled. The impact of individual measures to reduce the cardiovascular risk should be evaluated further.
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PMID:Change in atherosclerosis progression in HIV-infected patients: ANRS Aquitaine Cohort, 1999-2004. 1582

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

Calcium is a common component of an atherosclerotic plaque; therefore, the presence of coronary artery calcium (CAC) indicates atherosclerosis. This study investigated the difference in total CAC scores between HIV-infected patients treated with highly active antiretroviral therapy (HAART) and HIV-negative age-matched controls. HIV patients were 27 men treated with a protease inhibitor-containing HAART regimen for more than 1 year (M = 4.92 years, SD = 2.02), aged 30 to 60 years (M = 43.52 years, SD = 6.65), and not receiving lipid-lowering or hypoglycemic drugs. Controls were age-matched men randomly selected (three controls to one case, for a total of 81 controls) from our existing database of 25,250 men who self-referred for CAC screening (control database). Electron beam tomography was used to obtain CAC scores. The CAC scores were coded as above or below the age-specific (stratified in 5-year increments) 10th, 25th, 50th, 75th, or 90th percentile of our control database. Chi-square analyses for two independent samples indicated (1) a larger frequency of controls with CAC scores above the 10th (chi1= 8.32, P = .004) and 25th (chi1= 5.45, P = .02) percentiles than that of HIV patients, (2) no differences in CAC scores between groups above the 50th (chi = 0.85, P = .357) or 75th (chi = 0.46, P = .497) percentile, and (3) a larger frequency of HIV patients who were above the 90th percentile (chi = 4.5, P = .034). The strength of the relationship between group membership and scoring above the 90th percentile was significant (phi = 0.20, P = .034). These results tentatively suggest that there is an elevated level of subclinical atherosclerosis in HIV patients treated with HAART.
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PMID:Coronary artery calcium in HIV-infected men treated with highly active antiretroviral therapy. 1587 May 84

Noninvasive assessment of vascular dysfunction in the pediatric population has taken advantage of the development of high-resolution ultrasound techniques. The most frequently used methods are the quantification of flow-mediated endothelium-dependent dilation of the brachial artery and measurement of the intima-media thickening of the carotid artery. Both reduced flow-mediated dilation and increased intima-media thickness have been proven to correlate with late cardiovascular events and/or mortality in adults. As these noninvasive methods can easily be applied in children, there have been recent investigations in high-risk pediatric patients harboring classical cardiovascular risk factors. Endothelial dysfunction and increased thickness of the intima media are currently observed in children with familial hypercholesterolemia, obesity, and type 1 diabetes mellitus. The association of early vascular dysfunction with a known risk factor is an important issue as these anomalies precede the formation of atherosclerotic plaques. Therefore, they may help in stratification of the risk for cardiovascular event and to better tailor therapeutic interventions in at risk children. Finally, these methods have been applied in specific pediatric populations, such as children with end-stage renal disease, chronic parenteral nutrition, HIV infection, and coarctation of the aorta. In these conditions, endothelial dysfunction and vascular remodeling are also present early in life and these data raise new possibilities in the understanding of the pathogenesis of atherosclerosis in these populations.
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PMID:Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children. 1605 29


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