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)

Ritonavir-boosted protease inhibitor (PI) regimens have provided substantial benefits in the treatment of HIV/AIDS, resulting in improved clinical outcomes. However, treatment toxicities often affect adherence and may influence outcomes. Dyslipidemia is highly prevalent in many patients who receive a boosted PI regimen. The mechanism underlying dyslipidemia is probably multifactorial and may differ among the individual PIs. The prevalence of cardiovascular disease and events appears to be higher in patients treated with boosted PIs, and as long-term survival increases in HIV-infected persons, the long-term effect of dyslipidemia becomes a growing concern. The practitioner must consider the possibility of these adverse effects when choosing the antiretroviral regimen that best suits each patient. Until future studies define the optimal approach, an evaluation of cardiovascular risk factors and treatment of those risk factors according to evidence-based guidelines are warranted.
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PMID:Ritonavir-boosted protease inhibitors, Part 2: cardiac implications of lipid alterations. 1626 69

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

To understand the molecular mechanisms underlying the development of dyslipidemia and lipodystrophy that occurs after administration of aspartic acid protease inhibitors, we examined transcriptional profiles using cDNA microarrays in 3T3-L1 adipocytes exposed to 10 micromol/l ritonavir for 2-21 days. The expression levels of approximately 12,000 transcripts were assessed using the MgU74Av2 mouse microarray chip. Ritonavir altered gene expression of inflammatory cytokines, stress response genes localized to endoplasmic reticulum, oxidative stress genes, apoptosis-related genes, and expression of genes involved in cell adhesion and extracellular matrix remodeling. Microarray analysis also identified a novel gene downregulated by ritonavir, Cidea, whose expression levels may affect free-fatty acid metabolism. These changes suggest a unique, stress-related pattern in adipocytes induced by chronic exposure to the protease inhibitor, ritonavir.
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PMID:Effects of ritonavir on adipocyte gene expression: evidence for a stress-related response. 1871 45

The advent of combination antiretroviral therapy has led to significant improvement in the care of HIV-infected patients. Originally designed as a protease inhibitor (PI), ritonavir is currently exclusively used as a pharmacokinetic enhancer of other protease inhibitors, predominantly due to ritonavir's potent inhibition of the cytochrome P450 3A4 isoenzyme. Ritonavir-boosting of PIs decrease pill burden and frequency of dosing. Boosted PIs are recommended for first-line therapy in treatment and play a key role in the management of treatment-experienced patients. Potential problems associated with PIs include metabolic abnormalities (e.g. dyslipidemia), increased cardiovascular risk, and drug interactions.
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PMID:Ritonavir-boosted protease inhibitors in HIV therapy. 2150 Oct 34