Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular 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) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in peripheral artery and coronary artery diseases. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. 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.
Cardiovasc Res 2003 Oct 15
PMID:HIV infection, highly active antiretroviral therapy and the cardiovascular system. 1452 10

Controlled clinical studies and clinical experience over many years have proven that virtually all patients benefit from lipid-lowering therapy with statins, even those with normal LDL cholesterol levels. Several recent large outcome trials have further demonstrated the clinical benefits and safety of statins in patients with a wide-range of high risks for cardiovascular disease. Those patients at highest absolute cardiovascular risk generally have the most to gain from statin therapy. A variety of statins are available to lower plasma lipids to guideline levels, but all differ in their pharmacokinetic properties, drug interaction profiles, and risk of myotoxicity. This has been highlighted by the withdrawal of cerivastatin from the market as a result of serious safety concerns. This review examines the safety and effectiveness of statins in special populations at high risk of cardiovascular disease-patients with coronary heart disease, dyslipidaemia, diabetes, hypertension, nephrotic disease, HIV, organ transplant patients and the elderly-with a focus on clinically relevant differences in the properties of individual statins that may influence the risk of drug interactions and side effects.
Cardiovasc Drugs Ther 2003 May
PMID:The safety of HMG-CoA reductase inhibitors in special populations at high cardiovascular risk. 1457 85

The primary objective of this study was to review and summarise the literature on the spectrum and management of cardiac disease in HIV-infected people living in Africa. We searched MEDLINE (January 1980 to February 2003), reference lists of papers, and reviews on the subject, and contacted experts working in the field for information on relevant references. The review was limited to papers that were published in peer-reviewed journals and indexed on MEDLINE. Seventeen of the 21 studies identified met the inclusion criteria for analysis. The studies confirmed that cardiac abnormalities are more common in HIV-infected people, compare to normal controls, and that about half of hospitalized patients and a significant proportion of patients followed up over several years develop cardiac abnormalities. The commonest HIV-related cardiac abnormalities were cardiomyopathy and pericardial disease. Tuberculosis was the major cause of large pericardial effusion in Africa. Myocarditis was the commonest pathological abnormality in HIV-associated cardiomyopathy, and non-viral opportunistic infections such as toxoplasmosis and cryptococcosis may account for up to 50% of cases of HIV-associated cardiomyopathy in Africa. Echocardiography is indicated in HIV-positive patients with cardiac symptoms or signs. If cardiomyopathy or pericardial disease is identified, further investigation must be considered to exclude potentially treatable opportunistic infections. Further research in large numbers of patients is needed to determine the value of endomyocardial biopsy in the management of patients with HIV-associated cardiomyopathy, and to establish the place of adjuvant steroids in the treatment of HIV-associated tuberculous pericarditis.
Cardiovasc J S Afr
PMID:Cardiac involvement in HIV-infected people living in Africa: a review. 1461 Jun 10

Antiretroviral therapy has changed the face of the treatment of HIV throughout the world, converting a fatal into a chronic disease. HIV has reached disastrous levels of infection in southern Africa, and increased use of life-saving therapy is being implemented. The antiretrovirals have a variety of metabolic side effects that have been implicated in cardiovascular disease in other populations. This article discusses the impact of HIV on southern Africa, the metabolic and cardiac complications of both HIV and antiretrovirals, and strategies for dealing with drug side effects.
Cardiovasc J S Afr
PMID:The cardiovascular consequences of HIV and antiretroviral therapy. 1461 Jun 9

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.
Am J Cardiovasc Drugs 2002
PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

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.
Expert Rev Cardiovasc Ther 2003 May
PMID:Hyperlipidemia in children with HIV infection: an emerging problem. 1503 Mar 4

We examined heart tissues of AIDS patients with or without HIV cardiomyopathy (HIVCM) by immunohistochemistry, in situ polymerase chain reaction, in situ riboprobe hybridization, and the TUNEL technique for apoptosis. In HIVCM tissues, only inflammatory cells, but not endothelial cells or cardiomyocytes, displayed HIV-1 DNA and RNA. However, macrophages, lymphocytes, and--in a patchy fashion--cardiomyocytes and endothelial cells exhibited virus envelope protein gp120. Macrophages infiltrated the myocardium in a perivascular fashion and expressed tumor necrosis factor family ligands; adjacent cardiomyocytes suffered apoptosis. In vitro HIV-1 strongly invaded neonatal rat ventricular myocytes (NRVMs) and coronary artery endothelial cells (CAECs) and induced microvilli but did not replicate. HIV-1, gp120, or Tat induced Erk 1/2 phosphorylation, activation of caspase-3, and apoptosis of NRVMs and CAECs; all of these were inhibited by a MAPK/ERK-kinase (MEK) inhibitor U0126. The pathogenesis of HIVCM involves HIV-1 replication in inflammatory cells and induction of cardiomyocyte apoptosis by (1) the extrinsic pathway through apoptotic ligands and (2) the intrinsic pathway through direct virus entry and gp120- and Tat-proapoptotic signaling.
Cardiovasc Toxicol 2004
PMID:HIV-1 induces cardiomyopathyby cardiomyocyte invasion and gp120, Tat, and cytokine apoptotic signaling. 1537 27

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature involving endothelial and vascular smooth muscle cell (VSMC) proliferation, vasoconstriction, right ventricular hypertrophy, and eventually, right heart failure and death. PAH occurs 1000-fold more frequently in HIV patients than in the general population. Although conventional HIV therapy with nucleoside reverse transcriptase inhibitors (NRTIs) leads to regression of PAH, highly active antiretroviral therapy (HAART; two NRTI plus a protease inhibitor) increases the incidence of HIV-associated PAH as much as twofold. Although there are relatively few models for PAH, previous reports indicate the disease can be initiated by endothelial injury and release of the mitogen endothelin-1 (ET-1). ET-1, in turn, stimulates VSMC proliferation. To determine whether HAART induces endothelial injury and release of cytokines like ET-1, we treated human umbilical vein endothelial cells with micromolar amounts of AZT (3'-azido-3'-deoxythymidine), the protease inhibitor indinavir, or AZT plus indinavir, and measured cell viability, mitochondrial function, and ET-1 release. Both AZT and indinavir induced marked decreases in cellular oxygen uptake, as well as increases in ET-1 release. Although the drugs had no apparent effect on proliferation in VSMCs alone, in cocultures of VSMCs plus endothelial cells, the drugs increased proliferation of both endothelial cells and VSMCs. Finally, when cocultures of endothelial cells and VSMCs were treated with BQ-123 and BQ-788, selective antagonists for ET(A) and ET(B) receptors, respectively, drug-induced proliferation of both VSMCs and endothelial cells was attenuated. These data thus suggest that HIV drug cocktails may exacerbate preexisting HIV-associated PAH by inducing endothelial mitochondrial dysfunction, in turn stimulating the release of ET-1, and ultimately, vascular cell proliferation.
Cardiovasc Toxicol 2004
PMID:Effects of HIV drug combinations on endothelin-1 and vascular cell proliferation. 1537 29

Cardiac toxicity has been associated with HIV infection and exposure to nucleoside reverse transcriptase inhibitors (NRTIs), but the role of the latter in the development of cardiac disease of HIV-infected patients is uncertain. To investigate the cardiotoxicity of transplacentally administered zidovudine (AZT) or AZT plus lamivudine (3TC) in the absence of HIV infection, we evaluated several biomarkers of cardiac mitochondrial structure and cardiac structure and function in a B6C3F1 mouse model. In utero exposure to AZT-3TC resulted in ultrastructural pathology, loss of mitochondria, and altered echocardiographic measurements in newborn mice. Cardiac pathology and dysfunction persisted into the adult life of female mice exposed in utero to AZT, as evidenced by significant dose-dependent heart enlargement, clusters of atypical mitochondria and myofibril alterations, significantly increased cytochrome c oxidase activity, and significantly higher numbers of mutations in mitochondrial tRNA genes compared with unexposed controls at 18 to 24 mo of age. These data led to the hypothesis that the long-term pathology of peri-natal exposure to these NRTIs is related to persistent mitochondrial DNA mutations in cardiac tissue; that is, the primary damage during drug treatment is mutational (as opposed to affecting polymerase gamma and/or other mitochondrial elements) and leads over time to delayed, progressive cardiotoxicity.
Cardiovasc Toxicol 2004
PMID:Persistence of mitochondrial toxicity in hearts of female B6C3F1 mice exposed in utero to 3'-azido-3'-deoxythymidine. 1537 30

Treatment of HIV with AZT (zidovudine) may have toxic side effects as a result of multiple mechanisms. It is known that patients with AIDS may suffer from magnesium deficiency (MgD). We studied selected biochemical and histopathologic consequences of AZT administration (0.7 mg/mL in drinking water) with concurrent Mg-deficient (20% of normal) diet in male C57Bl/6N mice for 3 wk. Significant decreases in red blood cell glutathione (GSH) were evident in the Mg-deficient mice with or without AZT treatment, suggesting compromised antioxidant capacity in the blood. Although MgD alone led to a 1.9-fold increase in plasma thromboxane B(2) (TXB(2), derived from the highly vasoconstrictive TXA(2)), AZT + MgD increased the TXB(2) level 3.5-fold. AZT (+/-MgD) provoked prominent hepatic damage expressed by distortion of lobular architecture, nuclear and cellular swelling, and inflammatory lesions and loss of hepatocytes. AZT alone caused mild cardiac lesions, resulting in partial cardiac fibrosis, especially in the atrium. AZT + MgD caused only scattered small-size cardiac lesions consisting of microscopic foci of inflammatory infiltrates in the ventricles but led to more prominent lesions, fibrosis, and scars in the atrium. MgD or AZT alone caused varying degrees of skeletal muscle degeneration; in combination, more intense degeneration and regeneration of muscle cells were evident. In conclusion, it is suggested that both the decreased blood GSH and elevated plasma TXA(2) might contribute, at least in part, to the aggravated pathological damages observed in the atrium and skeletal muscle of the AZT-treated Mg-deficient mice.
Cardiovasc Toxicol 2004
PMID:Cardiac pathologic effects of azidothymidine (AZT) in Mg-deficient mice. 1537 32


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