Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly active anti-retroviral therapies, which incorporate HIV protease inhibitors, resolve many AIDS-defining illnesses. However, patients receiving protease inhibitors develop a marked lipodystrophy and hyperlipidemia. Using cultured human and rat hepatoma cells and primary hepatocytes from transgenic mice, we demonstrate that protease inhibitor treatment inhibits proteasomal degradation of nascent apolipoprotein B, the principal protein component of triglyceride and cholesterol-rich plasma lipoproteins. Unexpectedly, protease inhibitors also inhibited the secretion of apolipoprotein B. This was associated with inhibition of cholesteryl-ester synthesis and microsomal triglyceride transfer-protein activity. However, in the presence of oleic acid, which stimulates neutral-lipid biosynthesis, protease-inhibitor treatment increased secretion of apolipoprotein B-lipoproteins above controls. These findings suggest a molecular basis for protease-inhibitor-associated hyperlipidemia, a serious adverse effect of an otherwise efficacious treatment for HIV infection.
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PMID:HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. 1192 15

Effective therapies are now available that can stop the progression of HIV infection and significantly delay the onset of AIDS. The "highly active antiretroviral therapy" (HAART) is a combination of potent antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors, that has a variety of serious side effects, including lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance as well as fat wasting in face and limbs. There is still an open debate that concerns the precise responsibility of HAART as well as metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. The similarities with multiple symmetric lipomatosis (MSL), in which mitochondria impairment plays a crucial role, lead to the hypothesis that drug-induced damages to mitochondrial DNA are able to alter mitochondria functionality to an extent that is similar to what occurs in MSL. In addition, several evidences indicate that HAART is also linked to a deregulated production of tumour necrosis factor-alpha, which uses mitochondria as intracellular targets. In this paper, we review data concerning the role of mitochondria in the pathogenesis of lipodystrophy, and advance a unifying hypothesis involving either direct or indirect effects of the drugs employed during HAART.
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PMID:Mitochondria in the pathogenesis of lipodystrophy induced by anti-HIV antiretroviral drugs: actors or bystanders? 1174 23

We examined the prevalence of HIV, general medical, and psychiatric comorbidities by age based on a recent multisite cohort of HIV infected veterans receiving care: the Veterans with HIV/AIDS 3 Site Study (VACS 3). VACS 3 includes 881 adult patients with HIV infection enrolled between June 1999 and July 2000. Providers reported their patients' CDC-defined HIV comorbidities, general medical comorbidities (based on Duke and Charlson comorbidity scales), and psychiatric comorbidity. Mean age of participants was 49 years and 54% were African-American. The most common HIV comorbidities were oral candidiasis (21%), peripheral neuropathy (16%), and herpes zoster (16%). The most common general medical comorbidities included chemical hepatitis (53%), hypertension (24%), and hyperlipidemia (17%). The mean number of HIV and general medical comorbidities experienced by patients were respectively 1.1 and 1.4 (P < .001). Older (> or = 50 years) HIV-infected patients experienced a greater number of general medical comorbidities than those < 50 years (respectively 1.7 versus 1.2, P < .001). There was no significant difference in mean HIV comorbidity number by age. Based on patient report, 46% had significant depressive symptoms (> or = 10 on 10-item CES-D) and 21% reported at-risk drinking (> or = 8 on AUDIT). Providers reported 32% of patients had anxiety, 4% mania, 4% schizophrenia, and 11% cognitive impairment/dementia. General medical and psychiatric comorbidities constituted a higher disease burden for HIV-infected veterans than HIV comorbidities. Whether these comorbidities are due to antiretroviral drug toxicity or are age or lifestyle-associated conditions, the substantial prevalence of these "non-HIV" comorbidities suggest an important role for general medical and psychiatric management of HIV-infected patients.
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PMID:General medical and psychiatric comorbidity among HIV-infected veterans in the post-HAART era. 1175 Feb 6

Chloroquine is a drug with over 60 years of safe clinical use in the treatment of malaria. The multiple mechanisms of chloroquine action have appeared to be useful in the therapy of many miscellaneous disorders well beyond its original antimalarial purposes. This paper is focused on the application of chloroquine for the treatment of malaria, porphyria cutanea tarda, rheumatoid arthritis, palindromic rheumatism and lupus. The possibility of the use of chloroquine in the therapy of other disorders such as diabetes mellitus, AIDS, hyperlipidemia, sarcoidosis, hypercalcemia, and melanoma is reviewed. Mechanisms of action of the drug as well as side effects on metabolism are discussed in view of recent discoveries.
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PMID:[Chloroquine--miscellaneous properties of the antimalarial drug]. 1210 61

Although treatment of children infected with HIV with protease inhibitors has improved the survival of these patients, various adverse side effects have been reported, including metabolic abnormalities, such as hyperlipidaemia. We describe a case of hip osteonecrosis in an adolescent with AIDS who was being treated with protease inhibitors. There is a possible relation with hyperlipidemia. F.M.G., white, 11 years old, AIDS A2, started to receive AZT and DDI when he was 7 years old. In April 1999, the patient had a significant increase in viral load and so the antiretroviral therapy was switched to d4T, 3TC and Ritonavir. Triglyceride plasma levels reached 460mg/dl after this switch and were always above the reference value. In December 1999, the patient complained of pain in the right hip. On physical examination, he had limited movement of this joint. Magnetic resonance imaging of the right hip showed flattening, deformity and fragmentation of the femoral head, compatible with osteonecrosis. Few cases of femoral head osteonecrosis have been associated with HIV infection, in the absence of the classic risk factors for osteonecrosis. Metabolic risk factors include hypertriglyceridaemia. The immunological disorders that occur in the HIV infection may predispose the patient to avascular osteonecrosis and metabolic disorders, particularly hypertriglyceridemia, while the use of protease inhibitors, may be considered an additional risk factor for osteonecrosis. Given the importance of premature diagnosis and to avoid complications of osteonecrosis, we recommend evaluation of musculoskeletal symptoms in children receiving protease inhibitors.
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PMID:Hyperlipidaemia a risk factor for femoral head osteonecrosis (Legg-Calv -Perthes-like disease) in children with AIDS: case report. 1214 52

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.
AIDS Patient Care STDS 2000 Jan
PMID:Simvastatin-induced rhabdomyolysis in an HIV-infected patient with coronary artery disease. 1224 Aug 78

Osteonecrosis has been increasingly associated with HIV disease throughout the 1990s, and the incidence appears to be rising. The hip is most commonly involved and often bilaterally. Although anecodotal reports suggest an association between osteonecrosis and highly active antiretroviral therapy, controlled epidemiologic studies do not support a direct link. Many patients with osteonecrosis have established risk factors, some of which may be related to HIV disease or its therapy, including corticosteroid use and hyperlipidemia. Alcoholism, hypercoagulability, megesterol acetate use, immune reconstitution, and other factors may also contribute. Plain radiographs and magnetic resonance imaging are the cornerstones of diagnosis. Management is dependent on the stage of bone disease and ranges from observation to total joint arthroplasty. Clinicians may help to prevent HIV-associated osteonecrosis by encouraging patients to limit their exposure to the established risk factors for the disease.
AIDS 2003 Jan 03
PMID:Osteonecrosis in HIV disease: epidemiology, etiologies, and clinical management. 1247 64

Fat redistribution (lipodystrophy) and metabolic anomalies are reported increasingly in HIV-infected patients being treated with protease inhibitors. The incidence of these side effects ranges from 5% to 75% in such patients, who often complain of spontaneous fat wasting in the face, arms, or legs, with or without central obesity. Hyperlipidemia and insulin resistance are almost always associated with lipodystrophy. We review the metabolic complications of antiretroviral therapies and discuss possible therapeutic interventions.
AIDS Read 1999 Jul
PMID:Metabolic effects of protease inhibitor therapy. 1273 15

Hypertriglyceridemia has frequently been found both in subjects with AIDS and in asymptomatic HIV-positive ones. In order to evaluate the importance of hyperlipemia as an index of the clinical evolution of HIV infection, the levels of triglycerides, total cholesterol and CD4 lymphocytes were determined over a period of 2 years in 8 haemophiliacs with AIDS, 13 asymptomatic HIV-positive and 45 HIV-negative haemophiliacs attending the Operative Unit of Coagulation Disorders of the University of Pisa. The mean concentration of triglycerides and incidence of hypertriglyceridemia were significantly higher in haemophiliacs with AIDS, compared with HIV-negative subjects (p<0.0001), while the triglycerides values of asymptomatic HIV-positives fell between those of the other groups. Cholesterol levels were lower in HIV-positive haemophiliacs and in those with AIDS compared with HIV-negatives. No correlation was found between triglyceride levels and those of CD4 lymphocytes.
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PMID:[The behaviour of plasma triglycerides and cholesterol in HIV positive haemophiliacs] 1276 87

During the past decade, a large number of new drugs for treating HIV and its complications have been developed. The increasingly sophisticated use of these drugs in combination has led to a marked reduction in HIV-related morbidity and mortality in countries where they are available. HIV/AIDS patients receiving treatment are now expected to live into old age. The beneficial effect of HIV treatment has resulted in an expanding population of persons living with HIV/AIDS who will need the care of an HIV specialist because of the complexity of the treatment regimens and the rapidly changing HIV/AIDS knowledge base. However, this growing and aging population will also benefit from the care of a primary care physician. The primary care generalist is in the best position to recognize and diagnose HIV infection, evaluate HIV risk in his or her patient population, and help prevent HIV infection in persons at risk. In patients known to be infected, the primary care generalist will be best able to manage hyperlipidemia, diabetes, cardiovascular disease, and other disorders of an aging population with an increased risk of these and other conditions. Patients with HIV infection frequently accumulate a large number of specialist physicians, and the unique ability of the primary care physician to monitor their care and act as a knowledgeable patient advocate is a great benefit to the patient.
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PMID:HIV disease in primary care. 1282 57


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