Vascular complications associated with use of HIV protease inhibitors

Vittecoq, D.; Escaut, L.; Monsuez, J.-J.

doi:10.1016/s0140-6736(05)78644-x

Cited by 110 publications

(53 citation statements)

References 3 publications

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“…1,2 Although the initial focus was primarily on the relationship between dyslipidemia associated with antiretroviral therapy (ART) and cardiovascular risk, a broader appreciation of the complex interplay between traditional risk factors for CVD and HIV infection has emerged more recently. Several groups of investigators have designed studies to examine various aspects of the relationship between HIV infection, traditional cardiovascular risk factors, ART, and short-and longer-term cardiovascular risk [3][4][5][6][7][8][9][10][11] (see also Working Group 1).…”

mentioning

confidence: 99%

Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy

Currier¹,

Lundgren²,

et al. 2008

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mentioning

confidence: 99%

Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy

Currier¹,

Lundgren²,

et al. 2008

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“…At the same time, plasma triacylglycerols are often grossly increased, sometimes dramatically, to levels at which pancreatitis is likely (Henry et al 1998b;Sullivan et al 1998). In addition, there are reports of premature atherosclerosis in individuals on HAART (Behrens et al 1998;Gallet et al 1998;Henry et al 1998a;Laurence, 1998;Vittecoq et al 1998). Thus, it appears that, although anti-retroviral treatment does result in clinical improvement in overall nutritional state, not all metabolic abnormalities are reversed, and patients on therapy may still require further investigation and management of their metabolic syndrome.…”

Section: Anti-retroviral Therapy and Nutritional Statementioning

confidence: 99%

Nutrition and immune function in human immunodeficiency virus infection

Macallan

1999

Proc. Nutr. Soc.

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The triad of human immunodeficiency virus (HIV) infection, nutritional status and immune function are intimately related, each factor having effects on the others. The dominant effect in this three-way relationship is the effect of HIV infection on nutritional status, an effect which, until the advent of potent anti-retroviral drugs, has been manifest primarily as wasting. Recently, more complex metabolic abnormalities have become apparent, particularly fat redistribution syndromes, hyperlipidaemia and hypercholesterolaemia. For the converse effect, the effect of nutritional state on HIV disease progression, there is good evidence that clinical outcome is poorer in individuals with compromised nutrition. However, the beneficial effects of nutritional support have been more difficult to demonstrate. For macronutrients, effective macronutrient supply improves survival in severely-malnourished individuals and may have beneficial effects in less-severely-affected individuals. Micronutrient deficiencies appear to be involved in modifying clinical HIV disease and may also be associated with enhanced mother-to-child transmission of virus, particularly in developing countries. Intervention trials in this setting are currently under way. In conclusion, the interaction of HIV infection and nutrition is of great importance not just because of the major impact that HIV infection has on nutritional state, but also because strategies to improve nutritional status, both quantitatively and qualitatively, may have a beneficial effect on the clinical and immunological course of the disease.

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“…Unfortunately, the use of HIV protease inhibitors (PI) has also been associated with several undesirable side effects, including peripheral fat wasting and excessive central fat deposition (lipodystrophy), overt hyperlipidemia, and insulin resistance (3)(4)(5)(6)(7). These abnormalities in lipid metabolism may also lead to the increased incidence of accelerated atherosclerosis in HIV patients (8,9). The mechanism by which PI therapy leads to lipid abnormalities remains unclear, thus limiting the options for effective treatment of HIV-infected individuals.…”

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confidence: 99%

HIV Protease Inhibitor Induces Fatty Acid and Sterol Biosynthesis in Liver and Adipose Tissues Due to the Accumulation of Activated Sterol Regulatory Element-binding Proteins in the Nucleus

Riddle¹,

Kuhel²,

Woollett³

et al. 2001

Journal of Biological Chemistry

202

132

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The mechanism by which human immunodeficiency virus (HIV) protease inhibitor therapy adversely induces lipodystrophy and hyperlipidemia has not been defined. This study explored the mechanism associated with the adverse effects of the prototype protease inhibitor ritonavir in mice. Ritonavir treatment increased plasma triglyceride and cholesterol levels through increased fatty acid and cholesterol biosynthesis in adipose and liver. Ritonavir treatment also resulted in hepatic steatosis and hepatomegaly. These abnormalities, which were especially pronounced after feeding a Western type high fat diet, were due to ritonavir-induced accumulation of the activated forms of sterol regulatory binding protein (SREBP)-1 and -2 in the nucleus of liver and adipose, resulting in elevated expression of lipid metabolism genes. Interestingly, protease inhibitor treatment did not alter SREBP mRNA levels in these tissues. Thus, the adverse lipid abnormalities associated with protease inhibitor therapy are caused by the constitutive induction of lipid biosynthesis in liver and adipose tissues due to the accumulation of activated SREBP in the nucleus.The discovery and use of protease inhibitor therapy has significantly reduced the morbidity and mortality of AIDS as a consequence of HIV 1 infection (1, 2). Unfortunately, the use of HIV protease inhibitors (PI) has also been associated with several undesirable side effects, including peripheral fat wasting and excessive central fat deposition (lipodystrophy), overt hyperlipidemia, and insulin resistance (3-7). These abnormalities in lipid metabolism may also lead to the increased incidence of accelerated atherosclerosis in HIV patients (8, 9). The mechanism by which PI therapy leads to lipid abnormalities remains unclear, thus limiting the options for effective treatment of HIV-infected individuals.The urgency of designing agents that are less likely to induce lipid disturbances has prompted numerous studies aimed at understanding the relationship between PI therapy and abnormalities in lipid metabolism and preadipocyte differentiation. However, cell culture studies have yielded conflicting results with the PI either suppressing (10 -12) or enhancing (13) preadipocyte differentiation in vitro. These studies also focused primarily on PI effects on transcription factors that are responsible for regulating lipid metabolism pathways and adipocyte differentiation genes, such as the peroxisome proliferator-activated receptor-␥ (14), the CCAAT/enhancer-binding protein (15), and the sterol regulatory element-binding protein-1 (SREBP-1) (16, 17). Very little attention was paid to PI effects on lipogenesis per se. Accordingly, the lipodystrophic and hyperlipidemic effects of PI in vivo have not been defined. Additionally, the contribution of different dietary nutrients on PIinduced lipid abnormalities has not been addressed.In this study, we examined the effect of ritonavir, a prototype PI that elicits potent lipid abnormalities in patients (18 -20), on lipogenesis and plasma lipid concentrati...

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Vascular complications associated with use of HIV protease inhibitors

Cited by 110 publications

References 3 publications

Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy

Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy

Nutrition and immune function in human immunodeficiency virus infection

HIV Protease Inhibitor Induces Fatty Acid and Sterol Biosynthesis in Liver and Adipose Tissues Due to the Accumulation of Activated Sterol Regulatory Element-binding Proteins in the Nucleus

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