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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Worldwide, infection with the human immunodeficiency virus (HIV) is increasing. At the same time, new treatments allow patients to live longer. Consequently, cardiovascular manifestations, most of which occur relatively late in the course of the infection, are becoming more frequent. Pericardial effusion, the most common cardiovascular manifestation of HIV infection, usually is small and causes no hemodynamic compromise or symptoms. It does, however, augur a grim prognosis, as do other cardiovascular conditions associated with the infection: myocarditis, dilated cardiomyopathy, pulmonary arterial hypertension, cardiac lymphoma, and Kaposi's sarcoma of the heart. Highly active antiretroviral therapy (HAART), especially when incorporating protease inhibitors, greatly improves overall outlook in these patients, but appears not only to cause a lipodystrophic syndrome, but to accelerate atherosclerotic cardiovascular disease by inducing glucose intolerance, frank diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, increased lipoprotein (a), and decreased HDL cholesterol. Recent ongoing prospective trials also are showing an association of HAART with increased coronary artery disease and myocardial infarction.
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PMID:Cardiovascular disease in patients infected with the human immunodeficiency virus. 1475 Jul 51

Atherosclerosis increases cardiovascular risk and the possibility of developing acute myocardial infarction (AMI) or stroke. Patients infected with human immunodeficiency virus (HIV) often present morphological and metabolic alterations (hypercholesterolemia, hypertriglyceridemia, insulin resistance, diabetes) that can increase vascular risk. The frequent coexistence of classic risk factors (atherogenic diet, smoking, physical inactivity, cocaine abuse), the progressive increase in mean age of HIV-1 infected patients, and the polymedication they receive make it difficult to estimate the direct effect that new therapies may have on cardiovascular risk. Retrospective clinical studies with diverse designs in large cohorts offer contradictory results for cardiovascular risk in the HIV-infected population. Longer observational periods are needed and the effect of other classic risk factors needs to be controlled, in order to establish the possible detrimental effect the new therapies may have on cardiovascular risk in this population.
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PMID:[Cardiovascular risk in patients with chronic HIV-1 infection: a controversy with therapeutic, clinical and prognostic implications]. 1475 7

The evolution of fasting glucose, triglyceride, and total and high-density lipoprotein (HDL) cholesterol level and the factors associated with development of clinically significant abnormalities in these metabolic parameters at 6 months were assessed in 353 consecutive human immunodeficiency virus (HIV)-infected patients who were receiving antiretroviral therapy containing lopinavir-ritonavir. Although glucose and HDL cholesterol levels did not change, triglyceride and total cholesterol levels significantly increased (P<.0001 for each), as did the proportion of patients with a triglyceride level of >400 mg/dL and a total cholesterol level of >240 mg/dL (P=.002). A baseline triglyceride level of >400 mg/dL and a baseline total cholesterol level of >240 mg/dL were identified as independent factors predicting clinically significant hypertriglyceridemia and hypercholesterolemia, respectively, at 6 months. These findings may have clinical implications when the therapeutic option of lopinavir-ritonavir is considered.
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PMID:Risk of metabolic abnormalities in patients infected with HIV receiving antiretroviral therapy that contains lopinavir-ritonavir. 1503 36

Allograft dysfunction remains a major problem for long-term graft survival after kidney and heart transplantation. Current immunosuppressive regimens do not completely address the causes of allograft dysfunction which include acute rejection episodes, complications of immunodeficiency (for example, cytomegalovirus infection), nephrotoxicity from calcineurin inhibitors (cyclosporine and tacrolimus) and vascular remodeling and vasculopathy. Everolimus is a potent immunosuppressor that inhibits growth factor-stimulated proliferation of hematopoietic and nonhematopoietic cells, including vascular smooth muscle. Everolimus is indicated for the prophylaxis of acute rejection in kidney and heart transplant patients in a combined regimen with cyclosporine microemulsion and corticosteroids. Everolimus is formulated as both a tablet and a tablet for oral solution. It is rapidly absorbed and displays dose-proportional, stable pharmacokinetics. Everolimus has equivalent efficacy to mycophenolate mofetil in reducing the incidence of acute rejection after renal transplantation and superior efficacy to azathioprine after heart transplantation. Combination of everolimus with cyclosporine allows dose-reduction of cyclosporine while maintaining efficacy due to the synergistic immunosuppressive effects of the combination. Everolimus reduces intimal thickening of blood vessels to the graft and the incidence of allograft vasculopathy in heart transplantation. In both kidney and heart transplantation, the incidence of cytomegalovirus infection was lower in everolimus-treated patients compared with patients receiving the control treatment. Everolimus-related adverse events include elevated cholesterol and triglycerides, which respond to treatment, and decreased platelet count, which is transient. Nephrotoxicity may result from the combination of everolimus with full-dose cyclosporine but is mitigated by reducing the dose of cyclosporine. Everolimus is initiated at 0.75 mg b.i.d. with dose adjustments guided by therapeutic drug monitoring of predose blood levels. In clinical development trials, everolimus has demonstrated the ability to reduce the incidence of acute rejection episodes, cytomegalovirus infection and cardiac vasculopathy, thus addressing the primary causes of allograft dysfunction.
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PMID:Everolimus: a proliferation signal inhibitor targeting primary causes of allograft dysfunction. 1504 32

Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft-associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation. Rho GTPase activity can be negatively regulated by statins, a family of drugs used to treat hypercholesterolemia in man. Statins mediate inhibition of Rho GTPases by impeding prenylation of small G proteins through blockade of 3-hydroxy-3-methylglutaryl coenzyme A reductase. We show that statins decreased viral load and increased CD4+ cell counts in acute infection models and in chronically HIV-1-infected patients. Viral entry and exit was reduced in statin-treated cells, and inhibition was blocked by the addition of l-mevalonate or of geranylgeranylpyrophosphate, but not by cholesterol. Cell treatment with a geranylgeranyl transferase inhibitor, but not a farnesyl transferase inhibitor, specifically inhibited entry of HIV-1-pseudotyped viruses. Statins blocked Rho-A activation induced by HIV-1 binding to target cells, and expression of the dominant negative mutant RhoN19 inhibited HIV-1 envelope fusion with target cell membranes, reducing cell infection rates. We suggest that statins have direct anti-HIV-1 effects by targeting Rho.
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PMID:Statins inhibit HIV-1 infection by down-regulating Rho activity. 1531 78

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

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.
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PMID:Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction. 1618 Nov 44

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p < 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p < 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p < 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol.
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PMID:Gender-specific effects of HIV protease inhibitors on body mass in mice. 1747 47

Tipranavir is a recently approved nonpeptidic protease inhibitor specifically developed for the management of human immunodeficiency virus (HIV) infection in treatment-experienced patients with protease inhibitor-resistant infection. It is active against a wide range of drug-resistant laboratory- and patient-derived isolates. Tipranavir requires pharmacokinetic boosting by ritonavir (200 mg) to achieve therapeutic levels with twice-daily dosing and must be administered with food for optimal absorption. It is a potent protease inhibitor with a unique drug-resistance profile that offers advantages in the management of cases of multidrug-resistant HIV infection. Tipranavir (in combination with ritonavir) is both an inhibitor and inducer of cytochrome p450, with significant potential for drug-drug interactions, and therefore, it must be used cautiously when administered to patients who are receiving other drugs. Evolution of drug resistance after treatment failure with tipranavir is complex and is not yet fully understood. There is limited overlap in the resistance mutations that predict response to tipranavir and another new protease inhibitor, darunavir, which is active against drug-resistant isolates. Tipranavir is associated with elevations in alanine aminotransferase and aspartate aminotransferase levels, as well as elevated cholesterol and triglyceride levels, and can cause the typical gastrointestinal adverse effects associated with all protease inhibitors.
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PMID:Tipranavir: a new option for the treatment of drug-resistant HIV infection. 1771 62

The introduction of highly active antiretroviral therapy (HAART) has dramatically improved the long-term prognosis of human immunodeficiency virus (HIV)-infected patients, but several abnormalities of lipid and glucose metabolism have recently been reported with increasing frequency in patients receiving potent new antiretroviral combinations. Although a rare occurrence before the HAART era, insulin resistance has now been described as an important component of the lipodystrophy syndrome, including body fat redistribution, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia, and hyperglycemia. The etiology of such abnormalities remains unclear; but protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors are believed to contribute to the pathogenetic mechanism. The potential clinico-pathological consequences of glucose metabolism dysregulation, such as atherosclerosis and coronary heart disease, all make the management of insulin resistance and diabetes mellitus a challenge in the management of HIV-infected patients. Because of similarities to pathogenesis and clinical presentation of type 2 diabetes mellitus, treatment of HAART-associated hyperinsulinemia and hyperglycemia could follow the recommendations of the American Diabetes Association, but the most effective and safe management of these metabolic alterations is still unknown. The present review evaluated the most recently published data about incidence, risk factors, pathogenesis, clinical complications, and management of glucose disorders associated with antiretroviral therapy.
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PMID:Insulin Resistance and Diabetes Mellitus in HIV-Infected Patients Receiving Antiretroviral Therapy. 1837 Jun 93


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