Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0242339 (dyslipidemia)
13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic abnormalities associated with the treatment of human immunodeficiency virus (HIV) infection are well-recognized problems that increase cardiovascular risk. As a result of the complexity of treating both HIV- and antiretroviral-related comorbidities, strategies that improve adverse drug events while maintaining viral control are in critical need. Although guidelines have somewhat helped in the general approach and in first-line strategies for managing dyslipidemia in patients receiving antiretrovirals, a paucity of data exist to guide clinicians in treating patients whose conditions are refractory to first-line options or who are at substantial risk for cardiovascular events. Further complicating the choice of lipid-lowering strategy is the lack of randomized controlled data from the HIV-affected population and a concern about clinically significant drug-drug interactions. We describe an HIV-infected patient with efavirenz-associated dyslipidemia at very high cardiovascular risk who had not achieved his primary or secondary lipid goals despite 2 years of treatment in a lipid specialty clinic. Lipid control was accomplished in 10 weeks with a targeted, stepwise approach of switching efavirenz to nevirapine, followed by rosuvastatin 20 mg/day, which was sustained for at least 10 months. Of most importance, this outcome was achieved without any clinically significant alteration in virologic or immunologic control. This case report highlights the potential for a pharmacist-guided, multistep approach that addresses HIV-related dyslipidemia and incorporates the pharmacokinetic literature to guide lipid-lowering therapy and promote the attainment of goals based on current standards of care.
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PMID:A multimodal, evidence-based approach to achieve lipid targets in the treatment of antiretroviral-associated dyslipidemia: case report and review of the literature. 1857 8

Human immunodeficiency virus (HIV) is now a pandemic. It afflicts multiple organs, including the cardiovascular system. This occurs by direct invasion as well as opportunistic infections complicating acquired immunodeficiency syndrome. The presence of newer highly active antiretroviral therapy has led to longer survival of patients infected with HIV, but the cardiac abnormalities related to HIV have remained less well characterized. It is now evident that cardiac involvement in patients with acquired immunodeficiency syndrome is relatively common. This includes coronary artery disease, dilated cardiomyopathy, pericardial effusion, pulmonary hypertension, and ill effects of highly active antiretroviral therapy in the form of lipodystrophy, lipoatrophy, and dyslipidemia. In fact, HIV can now be viewed as a potential risk factor for coronary artery disease, and the dilemma facing clinicians is how to quantify this risk. Awareness of accelerated coronary artery disease and dilated cardiomyopathy is critical to implement preventive measures early in the course of HIV. However, better guidelines are still needed on the basis of prospective randomized controlled studies involving large populations. In conclusion, this review describes cardiac abnormalities associated with HIV, including possible molecular mechanisms. The co-morbid sequelae, their presentation, and pharmacologic management are also discussed.
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PMID:Cardiovascular manifestations in human immunodeficiency virus-infected patients. 1912 56

With the introduction of combination antiretroviral therapy, there have been substantial declines in both morbidity and mortality associated with human immunodeficiency virus (HIV)-1 infection. However, data increasingly indicate that HIV-1-infected individuals are faced with accelerated rates of chronic diseases that afflict the general population such as diabetes mellitus, hypertension, and dyslipidemia, as well as cardiovascular, liver, and kidney diseases. Furthermore, this population is exposed to a variety of adverse effects from long-term use of antiretroviral medications, which may cause clinically important renal toxicities. However, it often is challenging to distinguish antiretroviral-related renal toxicity from either direct effects of HIV-1 on the kidney or from a multitude of non-HIV-related kidney diseases. A timely and coordinated effort by the HIV primary provider and a nephrologist is likely to facilitate the evaluation of HIV-1-infected patients with new kidney problems.
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PMID:Antiretroviral nephrotoxicities. 1901 27

Human immunodeficiency virus (HIV) infection has become a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Metabolic complications such as dyslipidemia, insulin resistance, diabetes mellitus, obesity, and fat distribution abnormalities are associated with increased risk of cardiovascular disease. Cardiovascular disease is now a leading cause of death among HIV-infected patients. Lipid abnormalities, now often characteristically seen with HIV infection, include elevated triglycerides and low elevated total cholesterol (TC), and low high-density lipoprotein (HDL) levels of total and HDL cholesterol. Many antiretroviral drugs are associated with lipid abnormalities, which commonly include hypertriglyceridemia and increased total and low-density lipoprotein cholesterol levels. The management of dyslipidemia includes lifestyle modifications, lipid-lowering therapy, and switching antiretroviral therapy (ART). The increased prevalence of insulin resistance, impaired glucose tolerance, and diabetes is multifactorial in etiology. Management and goals of diabetes should follow the same practice guidelines in non-HIV-infected patients. Drug interactions and switching ART are additional management measures in diabetic HIV-infected patients. Since the treatment of lipodystrophy is a challenge, its prevention by selecting appropriate ART is the key.
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PMID:Diagnosis and management of common chronic metabolic complications in HIV-infected patients. 1902 Mar 62

The introduction of highly active antiretroviral therapy (HAART) for the treatment of acquired immunodeficiency syndrome (AIDS) has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV). However, the use of these drugs has been associated with lipodystrophic syndrome (LS), which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis) and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body), lipoatrophy (loss of fat in the extremities, face and buttocks) and mixed (lipohipertrophy + lipoatrophy). Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.
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PMID:Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus. 1903 Jul 39

Patients living with the human immunodeficiency virus (HIV) are at risk for dyslipidemia as a result of the disease itself and from certain classes of antiretroviral therapy. The protease inhibitors and non-nucleoside reverse transcription inhibitors have been associated with elevated triglycerides, total, and low-density lipoprotein cholesterol with decreased high-density lipoprotein. These classes of medications affect the cytochrome P450 (CYP) enzyme resulting in both induction and inhibition of numerous CYP enzymes. The statins are extensively metabolized by the CYP system and therefore drug-drug interactions between the statins and antiretroviral therapy must be considered when treating HIV or antiretroviral drug-induced dyslipidemia.
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PMID:Antiretroviral and statin drug-drug interactions. 1909 70

The successful introduction of highly active antiretroviral therapy (HAART), a combination of potent antiretroviral agents, including protease inhibitors, nucleoside reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors, has impacted positively on morbidity and mortality among human immunodeficiency virus (HIV)-positive patients. Over time, HAART has been associated with a number of metabolic and anthropometric abnormalities, including dyslipidemia and insulin resistance as well as subcutaneous fat loss and abdominal obesity, potentially contributing to cardiovascular risk. Recent studies have more firmly established that both HIV infection and HAART might increase the risk of clinical cardiovascular events. Furthermore, whereas HIV/HAART is associated with multiple aspects of endocrine dysfunction, there has been less focus on bone disease, although some studies indicate a higher prevalence of osteoporosis among HIV-positive subjects compared to HIV-negative controls. The relationship between bone and fat metabolism under HIV-positive conditions deserves further attention, and available data suggest the possibility of an intriguing connection. In the future, an increasing population of aging HIV-positive patients with a spectrum of antiretroviral therapies and accumulation of endocrine abnormalities and conventional cardiovascular risk factors will present preventive and therapeutic challenges to our health-care system.
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PMID:Human immunodeficiency virus and highly active antiretroviral therapy-associated metabolic disorders and risk factors for cardiovascular disease. 1935 10

Left ventricular hypertrophy (LVH) is an independent predictor of major cardiovascular events. Cardiovascular risk is increased among human immunodeficiency virus (HIV)-infected patients. To assess LV mass/hypertrophy in HIV infection, 654 women enrolled in the Women's Interagency HIV Study underwent transthoracic echocardiography. There were 454 HIV-infected and 200 uninfected women, mean age 40.8 +/- 9.3 years. LV mass/height(2.7) was similar between the HIV-infected and the HIV-uninfected groups (41.4 +/- 11.1 vs. 39.9 +/- 10.3 g/h(2.7); p = 0.37). The prevalence of LVH was similar between the two groups (LVH by LV mass/height(2.7) criteria 15.0% vs. 13.0%, p = 0.29). Relative wall thickness (RWT), defined as the ratio of LV wall thickness to cavity diameter, was also similar between the HIV-infected and HIV-uninfected groups (0.36 +/- 0.05 vs. 0.37 +/- 0.06, p = 0.16). On multiple linear regression analysis adjusting for age, W/H ratio, triceps skinfold thickness, systolic/diastolic BP, diabetes, hypertension and dyslipidemia; HIV status (b = 2.08, p = 0.02, CI 0.27-3.88); weight (b per kg = 0.15, p < 0.01, CI 0.08-0.22); and smoking duration (b per one-year increase = 0.08, p = 0.03, CI 0.01-0.16) were independent correlates of LV mass/height(2.7) (Model R(2) = 0.20, p < 0.001). Weight (aOR = 1.04, CI 1.01-1.06) and smoking duration (aOR = 1.03, CI 1.01-1.06) were independent correlates of LVH. Being HIV negative, increased age, increased triceps skinfold thickness, and higher W/H ratio were independent correlates of higher RWT. Among HIV-infected women, higher LV mass was not associated with a history of AIDS-defining illness, nadir CD4(+) count <200 cells/microl, or with the duration of highly active antiretroviral therapy (HAART). Women taking NRTIs had higher LV mass. Higher RWT was associated with current CD4(+) count. In conclusion, HIV infection is associated with greater LV mass but not with a higher prevalence of LVH. Among HIV-infected women, RWT, but not LV mass, is associated with the degree of immunosuppression.
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PMID:The association of HIV infection with left ventricular mass/hypertrophy. 1939 99

Protease inhibitors (PIs) inhibit the cytochrome P450 CYP3A4. Because the metabolism of pravastatin is independent of the cytochrome P450 CYP3A4, this drug has become the preferred statin for treatment of dyslipidemia associated with human immunodeficiency virus (HIV) infection, with no cases of serious toxicity such as rhabdomyolysis reported to date. We report an HIV-infected patient receiving antiretroviral regimen consisting of atazanavir, ritonavir, emtricitabine and tenofovir who developed severe rhabdomyolysis approximately 4 months after increasing his pravastatin dose from 40 to 80 mg daily. His symptoms resolved within 10 days after the discontinuation of pravastatin and antiretroviral therapy. To our knowledge, this is the first case of rhabdomyolysis possibly caused by pravastatin in an HIV-infected patient.
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PMID:Rhabdomyolysis in an HIV-infected patient on anti-retroviral therapy precipitated by high-dose pravastatin. 1944 5

Metabolic syndrome (MetS) is a cluster of risk factors, including elevated mean arterial pressure (MAP), atherogenic dyslipidemia (elevated triglycerides [TRG]), abdominal obesity (increased body mass index [BMI]), glucose intolerance (elevated glucose [GLU]), and prothrombotic/inflammatory state (increases in uric acid [UA]), that are associated with increased risk of cerebrovascular disease. We studied if an association existed between MetS components and human immunodeficiency virus (HIV)-associated cryptogenic strokes-those not caused by HIV complications, endocarditis, or stimulant abuse. We performed a retrospective case-control study. Eleven cryptogenic strokes were identified from 2346 HIV-infected (HIV+) participants. Each case was matched by age, sex, and date of stroke diagnosis to five HIV+ controls without stroke. Nonparametric stratified Wilcoxon ranked sum tests with subsequent mixed effect logistic regression determined the influence of each MetS component on HIV-associated cryptogenic stroke. Although each MetS component appeared higher for HIV+ cases with cryptogenic strokes than HIV+ controls, only MAP (odds ratio [OR] = 5.70, 95% confidence interval [CI] = 1.15-28.3) and UA (OR = 1.88, 95% CI = 1.06-3.32) were statistically different. A significantly higher percentage of HIV-associated cryptogenic stroke cases met criteria for MetS (4/11 = 36%) compared to HIV+ controls (6/55 = 11%). This observational study suggests a possible role for MetS components in HIV+ cryptogenic stroke cases. Although MetS is defined as a constellation of disorders, elevated hypertension and hyperuricemia may be involved in stroke pathogenesis. Reducing MetS component levels in HIV+ patients could therefore protect them from subsequent stroke.
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PMID:Role of metabolic syndrome components in human immunodeficiency virus-associated stroke. 1956 11


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