acipimox and Lipodystrophy

Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles?. Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice.. Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

Topics: Anti-HIV Agents; Cardiovascular Diseases; Cholesterol; Dyslipidemias; Growth Hormone-Releasing Hormone; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Lipodystrophy; Pyrazines; Risk Factors

Low-grade inflammation is a feature of chronic diseases such as type 2 diabetes and lipodystrophy. It is associated with abdominal adiposity, increased levels of NEFA, hyperinsulinaemia and low adiponectin levels. However, the causal relationship between impaired metabolism and inflammation is not understood. We explored the anti-lipolytic effect of acipimox and insulin on adiponectin and adipocyte-associated cytokines in patients with lipodystrophy.. In a randomised placebo-controlled crossover design using nine patients with non-diabetic, HIV-associated lipodystrophy, we assessed whether (1) overnight administration of a low dose of acipimox and/or (2) insulin-induced suppression of NEFA flux altered circulating plasma levels of adiponectin, IL-18, TNF-α and IL-6 in the basal condition and in a two-stage euglycaemic-hyperinsulinaemic clamp combined with stable isotopes (insulin infusion rates 20 mU m(-2) min(-1) and 50 mU m(-2) min(-1)).. Insulin decreased plasma NEFA in a dose-dependent manner (p < 0.0001). Acipimox reduced basal plasma NEFAs and plasma NEFAs during the low-dose insulin infusion compared with placebo (p < 0.0001 for acipimox effect). Plasma adiponectin and plasma IL-18 were reduced during both situations where lipolysis was inhibited (p < 0.0001 for acipimox effect; p < 0.0001 and p < 0.05 for insulin effect on plasma adiponectin and plasma IL-18, respectively). In contrast, plasma IL-6 and plasma TNF-α did not change during low NEFA concentrations.. Using two different tools to manipulate lipolysis, the present study found that acute inhibition of lipolysis reduces levels of adiponectin and IL-18 in patients with HIV-associated lipodystrophy.

Topics: Adiponectin; Cross-Over Studies; Female; Humans; Insulin; Interleukin-18; Lipodystrophy; Lipolysis; Male; Middle Aged; Pyrazines

Fatty acid concentrations are increased in patients with HIV and fat redistribution and may contribute to insulin resistance in this population.. We determined the effects of acute inhibition of lipolysis on insulin sensitivity in HIV-infected patients with fat redistribution who were receiving a protease inhibitor.. Seven HIV-infected men [age: 45 +/- 2 y; body mass index (in kg/m(2)): 28.8 +/- 1.9] with a fasting insulin concentration > or= 104 pmol/L (15 micro IU/mL), combined visceral adiposity and peripheral lipoatrophy, and receiving a protease inhibitor were studied. Tolbutamide-modified frequently sampled intravenous-glucose-tolerance tests (FSIGTTs) were performed after randomized double-blind administration of acipimox (500 mg at -90 and 0 min), a potent inhibitor of lipolysis, and placebo. The subjects completed 2 FSIGTTs separated by 3-7 d.. At baseline, fasting insulin and fatty acid concentrations were 27.6 +/- 5.0 micro IU/mL and 0.83 +/- 0.08 mmol/L (normal range: 0.1-0.6 mmol/L), respectively. Fatty acid concentrations were significantly reduced after acipimox compared with placebo (fatty acid area under the curve: acipimox = 73 +/- 8 compared with placebo = 122 +/- 12 mmol x 270 min/L, P = 0.002). Acipimox treatment resulted in a significant increase in the insulin sensitivity index (acipimox = 1.63 +/- 0.5 compared with placebo = 0.88 +/- 0.3 x 10(-4) x min(-1) x micro IU/mL, P = 0.015).. Acute inhibition of lipolysis and reduction in fatty acid concentrations are associated with improved insulin sensitivity in patients with HIV lipodystrophy and hyperinsulinemia. Further studies are needed to determine whether long-term antilipolytic strategies to reduce fatty acid concentrations may be useful in treating the metabolic disturbances associated with HIV lipodystrophy.

Topics: Adipose Tissue; Adult; Area Under Curve; Fasting; Fatty Acids; Glucose Tolerance Test; HIV Infections; Humans; Hyperinsulinism; Hypolipidemic Agents; Insulin Resistance; Lipodystrophy; Lipolysis; Male; Middle Aged; Protease Inhibitors; Pyrazines; Viscera