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)

The beneficial effects of antiretroviral therapy (ART) for the treatment of HIV disease have been accompanied by metabolic changes associated with an increased risk of cardiovascular disease. These changes, which include dyslipidemia, change in body fat distribution, and insulin resistance, resemble the symptoms of metabolic syndrome. Protease inhibitors, nucleoside analogue reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors have all been associated with dyslipidemia to varying degrees. In addition, patients on ART show an increased risk of myocardial infarction and other cardiovascular events. According to the recommendations of the National Cholesterol Education Program and the Adult AIDS Clinical Trial Group, health care providers should assess cardiovascular risk before starting ART and then continue to monitor lipid levels. Treatment of ART-associated dyslipidemia should follow the following sequence: therapeutic lifestyle changes, lipid-lowering drug therapy, and finally, modifying ART if necessary. By providing education, support, and follow-up care, nurse practitioners can help to implement these steps.
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PMID:The nurse practitioner's role in managing dyslipidemia and other cardiovascular risk factors in HIV-infected patients: impact of antiretroviral therapy. 1668 80

Our previous studies show that the depletion of cholesterol or sphingolipids (raft-associated lipids) from receptor-bearing adherent cell lines blocks HIV-1 entry and HIV-1 Env-mediated membrane fusion. Here we have evaluated the mechanism(s) by which these lipids contribute to the HIV-1 Env-mediated membrane fusion. We report the following: (1) GSL depletion from a suspension T lymphocyte cell line (Sup-T1) reduced subsequent fusion with HIV-1IIIB-expressing cells by 70%. (2) Cholesterol depletion from NIH3T3 cells bearing HIV-1 receptors (NIH3T3CD4R5/NIH3T3CD4X4) did not impair subsequent fusion with HeLa cells expressing the corresponding HIV-1 Envs. In contrast GSL depletion from these targets reduced fusion by 50% suggesting that GSL facilitate fusion in different ways. (3) GSL-deficient GM95 cells bearing high receptors fused with HIV-1 Env-expressing cells at 37 degrees C with kinetics similar to that of GSL + NIH3T3 targets. Based on these observations, we propose that the plasma membrane cholesterol is required to maintain the integrity of receptor pools whereas GSLs are involved in stabilizing the coupling of inter-receptor pools.
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PMID:Sphingolipids, cholesterol, and HIV-1: a paradigm in viral fusion. 1669 2

Macrophages play a central role in the pathogenesis of atherosclerosis and are also a host for a number of viruses, most importantly, HIV. Many viruses, including HIV, require cholesterol for their replication and as a structural element. Cholesterol also plays a pivotal role in innate antiviral immune responses. Although impairing innate immune response by increasing cell cholesterol content may be a deliberate strategy used by a pathogen to improve its infectivity, enhancing the risk of atherosclerosis is likely a byproduct. Consistent association between HIV infection and elevated risk of atherosclerosis suggested a connection between virus-induced changes in cholesterol metabolism and atherogenesis, but the mechanisms of such connection have not been identified. We describe in this review various mechanisms enabling viruses to exploit macrophage pathways of cholesterol metabolism, thus diverting cholesterol for a purpose of increasing viral replication and/or for altering innate immune responses. To alter the cellular cholesterol content, viruses "hijack" the pathways responsible for maintaining intracellular cholesterol metabolism. The damage to these pathways by viral infection may result in the inability of macrophages to control cholesterol accumulation and may lead to formation of foam cells, a characteristic feature of atherosclerosis. Further elucidation of the mechanisms connecting viral infection and macrophage cholesterol metabolism may be fruitful for developing approaches to treatment of atherosclerosis and viral diseases.
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PMID:Human immunodeficiency virus infection and macrophage cholesterol metabolism. 1705 63

The peripheral-type benzodiazepine receptor (PBR) is an 18 kDa mitochondrial membrane protein with still elusive function in cell death. Here, we studied whether PBR is involved in Ca2+-induced permeability transition pore (PTP) opening in isolated rat brain mitochondria (RBM). PTP opening is important in mitochondrial events leading to programmed cell death. Immunoblots revealed a single 18 kDa anti-PBR antibody-immunoreactive band in purified RBM. Adenine nucleotide transporter, a key PTP component, was found in the PBR-immunoprecipitate. In isolated intact RBM, addition of a specific anti-PBR antibody [H. Li, Z. Yao, B. Degenhardt, G. Teper, V. Papadopoulos, Cholesterol binding at the cholesterol recognition/interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 1267-1272] delayed Ca2+-induced dissipation of membrane potential (psi(m)) and diminished cyclosporine A-sensitive Ca2+ efflux, which are both indicative for the suppression of PTP opening. Moreover, anti-PBR antibody caused partial retention of Ca2+ in the mitochondrial matrix in spite of psi(m) dissipation, and reduced activation of respiratory rate at Ca2+-induced PTP opening. A release of pro-apoptotic factors, AIF and cytochrome c, from RBM was shown at threshold Ca2+ load. Anti-PBR antibody blocked the release of AIF but did not affect the cytochrome c release. Addition of ATP was able to initiate PTP closing, associated with psi(m) restoration and Ca2+ re-accumulation. At the same time mitochondrial protein phosphorylation (incorporation of 32P from [gamma-32P]ATP) occurred and anti-PBR antibody was able to inhibit phosphorylation of these proteins. The endogenous PBR ligand, protoporphyrin IX, facilitated PTP opening and phosphorylation of the mitochondrial proteins, thus, inducing effects opposite to anti-PBR antibody. This study provides evidence for PBR involvement in PTP opening, controlling the Ca2+-induced Ca2+ efflux, and AIF release from mitochondria, important stages of initiation of programmed cell death.
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PMID:The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. 1717 93

Dyslipidemia is a common metabolic complication among HIV-infected patients who receive protease inhibitor (PI)-based antiretroviral therapy (ART). In order to assess the prevalence of lipid abnormalities and related factors, a cross-sectional analytic study of the lipid profiles of 170 Thai adult HIV-infected patients receiving PI-containing HAART who attended the HIV-clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand between January and August 2005 was conducted. Studied subjects had a median age of 40 years with a median duration of taking PIs of 22.1 months. The mean serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were 259.7, 43.7, 135.2, and 506.8 mg/dl, respectively, and the mean TC:HDL-c ratio = 6.4. According to the US National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines, high TC, low HDL-c, high TC:HDL-c ratio, high LDL-c, and high TG were found in 52.4, 36.5, 18.8, 44.1, and 42.9%, respectively. Seventy-five subjects (44.1%) were taking lipid-lowering drugs. Only 54 subjects (31.8%) had baseline serum lipid profiles tested before beginning PI. There was statistically significant association between group of PI with serum TC and TG. Subjects taking double boosted and single boosted PI had significantly higher serum TC and TG levels than unboosted PI. Males had significantly higher serum TG levels, while females had significantly higher serum HDL-c levels. Age was significantly associated with serum TC, LDL-c levels, and TC:HDL-c ratios. Serum TC and LDL-c levels were also significantly higher in subjects taking efavirenz.
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PMID:Lipid profiles of Thai adult HIV-infected patients receiving protease inhibitors. 1753 49

Both HIV and its treatment, particularly protease inhibitors, can cause lipidemia similar to that seen with the metabolic syndrome. The most notable effects are elevated triglyceride levels and decreased high-density lipoprotein cholesterol levels, with or without elevated low-density lipoprotein cholesterol (LDL-C) levels. Current recommendations by the National Cholesterol Education Program for HIV-infected persons focus on LDL-C as the primary target of therapy: after lifestyle modifications, statins should be used to lower LDL-C levels. Therapy with fibrates is recommended to lower triglyceride levels. However, omega-3 fatty acids can be an effective means of lowering triglyceride levels as well, particularly in patients with markedly elevated triglyceride levels.
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PMID:Treatment of HIV-associated dyslipidemia: a role for omega-3 fatty acids. 1767 16

This retrospective cohort study conducted at the Durham Veterans Affairs Medical Center evaluated the effectiveness and safety of lipid-lowering therapy (LLT) in a HIV-infected population as compared with a general population with hyperlipidaemia. Fifty-three HIV-infected subjects who developed dyslipidaemia and 53 age-matched non-HIV-infected subjects receiving LLT were selected. Efficacy of LLT was assessed after three and six months. Non-HIV-infected subjects were more likely to achieve total cholesterol (TC) goals at three and six months (P = 0.045, P = 0.005) and triglyceride (TG) goals at six months (P = 0.017). Less than 45% of HIV-infected subjects met National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) goals at three or six months. While non-HIV-infected subjects were more likely to achieve TC and TG goals than HIV-infected subjects, overall achievement of NCEP III goals was poor. This result was likely due to treatment with inappropriately low doses of statins.
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PMID:A comparison of the effectiveness of lipid-lowering therapy between HIV- and non-HIV-infected subjects with hyperlipidaemia. 1807 21

Biological membranes are composed of many molecular species of lipids and proteins. These molecules do not mix ideally. In the plane of the membrane components are segregated into domains that are enriched in certain lipids and proteins. Cholesterol is a membrane lipid that is not uniformly distributed in the membrane. Proteins play an important role in determining cholesterol distribution. Certain types of protein lipidation are known to cause the lipoprotein to sequester with cholesterol and to stabilize cholesterol-rich domains. However, proteins that are excluded from such domains also contribute to the redistribution of cholesterol. One of the motifs that favor interaction with cholesterol is the CRAC motif. The role of the CRAC motif of the gp41 fusogenic protein of HIV is discussed. The distribution of the multianionic lipid, phosphatidylinositol(4,5)bis-phosphate (PtnIns(4,5)P2), is also not uniform in cell membranes. This lipid has several functions in the cell, including a morphological role in determining the sites of attachment of the actin cytoskeleton to the plasma membrane. PtnIns(4,5)P2 is sequestered by proteins having clusters of cationic residues in their sequence. Certain proteins containing cationic clusters also contain moieties such as myristoylation or a CRAC segment that would also endow them with the ability to sequester to a cholesterol-rich domain. These proteins interact with PtnIns(4,5)P2 in a cholesterol-dependent manner forming domains that are enriched in both cholesterol and in PtnIns(4,5)P2 but can also be distinct from liquid-ordered raft-like domains.
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PMID:Proteins and cholesterol-rich domains. 1842 71

A retrospective cohort study evaluating the frequency of and factors related to clinical inertia in low-density lipoprotein (LDL) management was performed. Subjects were 90 patients that were not meeting National Cholesterol Education Program Adult Treatment Panel III LDL goals at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic between 1 August 2004 and 1 August 2005. Clinical inertia was observed in 44% of cases. Patients with higher baseline LDL levels were less likely to experience inertia, whereas women and those in the highest coronary heart disease risk category were more likely to be affected.
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PMID:Clinical inertia in the management of low-density lipoprotein abnormalities in an HIV clinic. 1844 73

Macrophages are an important natural target cell for HIV-1, but previous studies of virus entry into these cells are limited, and the involvement of membrane cholesterol and lipid rafts is unknown. Cholesterol disruption of macrophage membranes using four pharmacological agents acting by different mechanisms: methyl-beta cyclodextrin, nystatin, filipin complex and Lovastatin, all significantly inhibited productive HIV entry and reverse transcription. The inhibitory effects of these drugs resulted in decreased virus release from infected cells, and could be substantially reversed by the addition of water-soluble cholesterol. The virus bound equally to cholesterol-disrupted cells even though HIV receptor expression levels were significantly reduced. Macrophage CD4 and CCR5 were found to partition with the detergent-resistant membranes with a typical raft-associating protein flotillin-1. HIV particles were observed co-localising with a marker of lipid rafts (CTB-FITC) early post infection. These data suggest that macrophage membrane cholesterol is essential for HIV entry, and implicate lipid raft involvement.
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PMID:HIV entry in macrophages is dependent on intact lipid rafts. 1918 99


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