Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Persons with human immunodeficiency virus (HIV) infection might be at risk for ischemic cardiovascular disease (CVD). We reviewed the records of 16 HIV-infected persons with proven CVD (8 cases of angina and 8 cases of myocardial infarctions). This represents 1.7% of HIV-infected persons seen at our institution from 1 April 1999 through 25 April 2000. In comparison with 32 HIV-infected age- and sex-matched controls, case patients had more risk factors for CVD (median number of risk factors for CVD, 3 versus 1; P<.001), lower nadir CD4+ lymphocyte counts (median, 101 cells/mm3 versus 278 cells/mm3; P=.02), and a longer duration of prior exposure to nucleoside analogs (median, 190 weeks versus 130 weeks; P=.02). There was no difference in the duration of exposure to protease inhibitors. Ischemic CVD occurs in HIV-infected persons and appears to be most closely associated with traditional risk factors for coronary artery disease (for example, hypertension and hypercholesterolemia). Lower CD4+ lymphocyte counts and duration of HIV infection might also be risk factors or markers for the development of ischemic CVD.
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PMID:Ischemic cardiovascular disease in persons with human immunodeficiency virus infection. 1217 41

The prevalence of silent myocardial ischemia (SMI) and the factors associated with SMI were evaluated in patients infected with human immunodeficiency virus (HIV) who had been receiving highly active antiretroviral therapy (HAART) for > or =12 months and did not have known coronary artery disease or cardiac symptoms. Patients prospectively underwent exercise stress testing. The prevalence of SMI was 11% (11 of 99 patients). Patients who had SMI were significantly older than were patients who did not (mean+/-SD, 51+/-8 years vs. 42+/-9 years; P=0.001) and were more likely to have trunk obesity (54% of patients vs. 17%; P=.004). A significant correlation was found between a positive exercise test result and obesity (correlation,.006), waist-to-hip ratio (.007), and glucose and cholesterol levels (.04; P=.03). In multivariate analysis, age, central fat accumulation, and cholesterol level were independent variables associated with the detection of SMI. Exercise testing might be recommended for patients with HIV who have central fat accumulation and hypercholesterolemia.
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PMID:Exercise stress testing for detection of silent myocardial ischemia in human immunodeficiency virus-infected patients receiving antiretroviral therapy. 1179 81

Examination of children with different noninfectious diseases resulted in obtaining the data base on the state of health of 201 children belonging to the potential risk group of the development of secondary immunodeficiency. The children were subdivided into several groups which differed by the type of immune disturbances and accompanying metabolic shifts. The level of antibodies to one of the fragments of peptidoglycan-N-acetylmuramyldipeptide was compared with the character of changes in the immune system. Different titers of serum antibodies to peptidoglycan were found to correspond to different forms of immune disturbances. The study showed that from the group with the absence of definite signs of immunodeficiency to the group with the pronounced deficiency of T lymphocytes and monocytes expressing CD14 antigen changes in the immune system increased in parallel to a rise in the concentration of alpha 2-macroglobulin, the development of hypercholesterolemia and a decreased level of antibodies to peptidoglycan. Opportunistic microflora was seemingly an important factor in the formation of definite forms of disturbances of the immune system and accompanying metabolic shifts.
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PMID:[Level of serum antibodies to opportunistic microflora as a marker of the secondary immunodeficiency processes in children]. 1187 2

As greater numbers of human immunodeficiency virus (HIV)-infected individuals live to middle-age and beyond, there is growing concern that elevated cholesterol and lipid values will lead to cardiovascular complications in such patients. Furthermore, several of the highly active antiretroviral therapies (HAART) used to reduce levels of circulating HIV and extend acquired immunodeficiency syndrome (AIDS)-related survival are associated with a rise in plasma lipids. Anecdotal reports suggest such rises may be linked to cardiovascular complications. Herein, we review the case of a 74-year-old HIV-infected man with advanced coronary artery disease. He was prescribed simvastatin for control of hyperlipidemia and within 4 weeks developed muscle pain, proximal muscle weakness, myoglobinuria, and a markedly elevated creatinine phosphokinase (CPK). Simvastatin was discontinued, and rhabdomyolysis improved rapidly with conservative care. This report emphasizes this rare, but potentially significant, side effect of statin anticholesterol agents. Medical providers who prescribe statins must remember to check CPK levels when their HIV-infected patients complain of muscle pain. Discontinuing the offending drug will usually result in rapid diminution of muscle pain and inflammation and improve muscle strength.
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PMID:Simvastatin-induced rhabdomyolysis in an HIV-infected patient with coronary artery disease. 1224 Aug 78

Vascular complications in the course of human immunodeficiency virus (HIV) infection are multifactorial and may be caused by the virus itself or by the related opportunistic infections and neoplasms. Highly active antiretroviral therapy (HAART), which dramatically modifies the natural history of HIV disease, causes in a high proportion of patients a metabolic syndrome that includes body fat redistribution, hypercholesterolaemia, hypertriglyceridaemia and insulin resistance. These effects are particularly evident in patients treated with protease inhibitors (PIs). However, studies on the cardiovascular risk among HIV-infected individuals receiving PIs have not shown a consistent association. The pathogenesis of the HAART-associated metabolic syndrome has not been completely elucidated, but there is growing evidence that a synergistic effect between PIs and nucleoside reverse transcriptase inhibitors might play a significant role. All HIV-infected patients candidate to antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk with the available guidelines.
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PMID:HIV infection, antiretroviral therapy and cardiovascular risk. 1239 24

Human immunodeficiency virus protease inhibitors are associated with metabolic abnormalities that may increase risk of atherosclerotic vascular disease, including dyslipidemia, insulin resistance, and central obesity. Dyslipidemia, characterized by hypercholesterolemia and hypertriglyceridemia, small low- and high-density lipoprotein particles, and in some cases lipoprotein(a) excess, can be severe and has been associated with endothelial dysfunction and carotid atherosclerosis. The mechanisms underlying protease inhibitor-associated dyslipidemia have not been elucidated completely, but appear to involve hepatic overproduction of very low-density lipoproteins and to a lesser extent, impaired clearance. Insulin resistance appears to mediate part of the adverse lipoprotein changes observed in patients taking protease inhibitors. Ongoing epidemiological and surrogate endpoint studies are investigating the atherogenicity of these medications. Until the risk associated with use of protease inhibitors is better understood, identifying patients at high risk for adverse vascular events such as heart attacks, cardiac death, and stroke is a high priority. This article reviews the lipid and lipoprotein abnormalities associated with use of protease inhibitors, possible mechanisms for protease inhibitor-associated dyslipidemia, its potential atherogenicity, and use of the National Cholesterol Education Program Adult Treatment Panel III Guidelines for the management of patients with dyslipidemia.
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PMID:Dyslipidemia in the era of HIV protease inhibitors. 1263 93

There is accumulating evidence that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) can induce hyperlipidaemia. To evaluate the frequency and type of hyperlipidaemia in PI-treated patients, 98 outpatients were prospectively analysed for their lipoprotein characteristics at the Medizinische Hochschule in Hannover, Germany. Fifty-seven percent of the patients studied presented with hyperlipidaemia. Both hypertrigylceridaemia (type IV and V hyperlipoproteinaemia, 33%) and hypercholesterolaemia (type IIa hyperlipoproteinaemia, 6%) were detectable. The remaining 18% had a type IIb hyperlipoproteinaemia. Increased lipid levels were highly statistically significant compared to a control group of PI-naive HIV-1-infected patients [low-density lipoprotein (LDL) 146 mg/dl (range, 53-274 mg/dl) versus 105 mg/dl (range, 22-188 mg/dl; P=0.0006); very-low-density lipoprotein (VLDL) 35.5 mg/dl (5-253 mg/dl) versus 18 mg/dl (range, 3-94 mg/dl; P=0.0002)]. All PIs used (saquinavir, indinavir, nelfinavir and ritonavir) were associated with this variable form of hyperlipidaemia according to the Fredrickson classification. There was no significant correlation of any determined lipid value with the duration of treatment. A higher frequency of the apolipoprotein E2 allele and E4 allele was observed in the hyperlipidaemic subjects. Patients with excessive hypertriglyceridaemia showed a reduced lipoprotein lipase activity. Lipodystrophy was observed especially in hyperlipidaemic patients and to a lesser extent in normolipidaemic subjects. The frequency of hyperlipidaemic risk factors was surprisingly high in the group studied, which in turn may explain the proposed increased risk of atherogenesis in HIV-1 PI-treated patients. Therefore, PI-treated subjects should also be evaluated for their lipoprotein pattern, which may require antihyperlipidaemic interventions.
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PMID:Lipid evaluation in HIV-1-positive patients treated with protease inhibitors. 1273 56

Inhibitors of the human immunodeficiency virus (HIV)-1 protease have proven to be effective antiretroviral drugs. However, patients receiving these drugs develop serious metabolic abnormalities, including hypercholesterolemia. The objective of the present study was to identify mechanisms by which HIV protease inhibitors increase plasma cholesterol levels. We hypothesized that HIV protease inhibitors may affect gene regulation of certain LDL receptor (LDLR) family members, thereby altering the catabolism of cholesterol-containing lipoproteins. In this present study we investigated the effect of several HIV protease inhibitors (ABT-378, Amprenavir, Indinavir, Nelfinavir, Ritonavir, and Saquinavir) on mRNA, protein, and functional levels of LDLR family members. Our results demonstrate that one of these drugs, Nelfinavir, significantly decreases LDLR and LDLR-related protein (LRP) mRNA and protein levels, resulting in the reduced functional activity of these two receptors. Nelfinavir exerts its effect by reducing levels of active SREBP1 in the nucleus. The finding that Nelfinavir reduces the levels of two key receptors (LRP and LDLR) involved in lipoprotein catabolism and maintenance of vessel wall integrity identifies a mechanism that causes hypercholesterolemia complications in HIV patients treated with this drug and raises concerns about the atherogenic nature of Nelfinavir.
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PMID:Modulation of the LDL receptor and LRP levels by HIV protease inhibitors. 1283 56

Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution or lipodystrophy, hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and diabetes mellitus have been extensively reported in subjects treated with protease inhibitor (PI)-based antiretroviral regimens. In particular, dyslipidaemia occurs in up to 70-80% of HIV-infected individuals receiving HAART and can be associated with all the available PIs, although hypertriglyceridaemia appears to be more frequent in patients treated with ritonavir, ritonavir-saquinavir, or ritonavir-lopinavir. The potential long-term consequences of HAART-associated hyperlipidaemia are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving PIs. Dietary changes, regular aerobic exercise and switching to a PI-sparing regimen may act favourably on dyslipidaemia. Lipid-lowering therapy is often required with statins or fibrates. The choice of hypolipidaemic drugs should take into account potential pharmacological interactions with antiretroviral agents.
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PMID:Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. 1464 23

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


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