Disorders of fat distribution in HIV infection

Shaw, Andrew J.; McLean, Ken; Evans, B A

doi:10.1258/0956462981921189

Cited by 56 publications

(22 citation statements)

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“…Antiretroviral therapy (ART) in HIV-infected patients is frequently associated with insulin resistance, dyslipidemia, lipodystrophy and in some cases diabetes mellitus [4,15,16,20,21,23,24]. The underlying pathophysiological mechanisms of these alterations are unknown.…”

Section: Introductionmentioning

confidence: 99%

Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus

et al. 1999

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Antiretroviral therapy (ART) is frequently associated with metabolic alterations, including insulin resistance and diabetes mellitus. In this pilot study, we evaluated the effect of the PPARgamma activator troglitazone on ART-associated insulin resistance in HIV-infected patients with ART-associated diabetes mellitus. Six patients with protease inhibitor (PI)-associated diabetes mellitus, lipodystrophy and dyslipidemia were treated with troglitazone 400 mg q.d. for 3 months. Previous oral antidiabetics were discontinued prior to the study. At baseline and after 3 months, insulin sensitivity (intravenous insulin tolerance test), body composition (multifrequence bioelectrical impedance analysis) and fat distribution (CT scan quantification) were assessed. Glycaemic control (fasting and postprandial blood glucose, fructosamine, glycosylated haemoglobin) and serum lipid status were determined monthly. In four of the six patients, there was a clear improvement in insulin sensitivity, resulting in a reversal of insulin resistance in two of these patients. Overall, there was an increase in lean body mass and a decrease in total body fat. The volume of visceral adipose tissue decreased whilst the volume of subcutaneous adipose tissue increased. Total cholesterol, LDL and HDL cholesterol increased, and total triglycerides and VLDL-cholesterol decreased. No adverse effects such as hepatotoxicity were observed. Treatment with troglitazone 400 mg q.d. can ameliorate and in some cases even reverse ART-associated insulin resistance. Therefore, further studies including non-diabetic patients with ART-associated insulin resistance may be helpful in evaluating the long-term effects of thiazolidinediones on ART-associated insulin resistance and other metabolic complications, such as adipose maldistribution and dyslipidaemia.

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Section: Introductionmentioning

confidence: 99%

Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus

et al. 1999

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“…The surprising feature of lipodystrophy syndrome is a difference in sensitivity to HAART between visceral and subcutaneous adipose tissues. In fact, under HAART, subcutaneous adipose tissue undergoes atrophy, whereas visceral adipose tissue does not (5,34). Although the use of NRTIs was originally believed to be secondary to the use of the protease inhibitor class, it is now clear that NRTIs are also involved in this syndrome (3,15).…”

mentioning

confidence: 99%

Site-Specific Reduction of Oxidative and Lipid Metabolism in Adipose Tissue of 3′-Azido-3′-Deoxythymidine-Treated Rats

Deveaud

Beauvoit

Reynaud

et al. 2007

Antimicrob Agents Chemother

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Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3-azido-3-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two ratecontrolling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy.

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“…Clin. Aspect Treatment HIV Infect., 1997; package insert for Sustiva [efavirenz]), and lipodystrophy (13,21) have been observed in HIV-positive patients. The etiology of these changes is poorly understood.…”

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confidence: 99%

Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin

Hsyu

Schultz-Smith

Lillibridge

et al. 2001

Antimicrob Agents Chemother

129

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3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are effective agents in lowering cholesterol and triglycerides and are being used by human immunodeficiency virus-positive patients to treat the lipid elevation that may be associated with antiretroviral therapy. Many HMG-CoA reductase inhibitors and protease inhibitors are metabolized by the same cytochrome P450 enzyme 3A4 (CYP3A4). In addition, many protease inhibitors are potent inhibitors of CYP3A4. Therefore, coadministration of these two classes of drugs may cause significant drug interactions. This open-label, multiple-dose study was performed to determine the interactions between nelfinavir, a protease inhibitor, and two HMG-CoA reductase inhibitors, atorvastatin and simvastatin, in healthy volunteers. Thirty-two healthy subjects received either atorvastatin calcium (10 mg once a day) or simvastatin (20 mg once a day) for the first 14 days of the study. Nelfinavir (1,250 mg twice a day) was added on days 15 to 28. Pharmacokinetic assessment was performed on days 14 and 28. The study drugs were well tolerated. Nelfinavir increased the steady-state area under the plasma concentration-time curve during one dosing period (AUC ) of atorvastatin 74% and the maximum concentration (C max ) of atorvastatin 122% and increased the AUC of simvastatin 505% and the C max of simvastatin 517%. Neither atorvastatin nor simvastatin appeared to alter the pharmacokinetics of nelfinavir. It is recommended that coadministration of simvastatin with nelfinavir should be avoided, whereas atorvastatin should be used with nelfinavir with caution.

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Disorders of fat distribution in HIV infection

Cited by 56 publications

References 0 publications

Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus

Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus

Site-Specific Reduction of Oxidative and Lipid Metabolism in Adipose Tissue of 3′-Azido-3′-Deoxythymidine-Treated Rats

Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin

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