Tesamorelin for the treatment of excess abdominal fat in HIV-1-infected patients with lipodystrophy

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Publisher: Expert Reviews Ltd.
Document Type: Article
Length: 6,332 words
Lexile Measure: 1490L

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Author(s): Maria Gracia Mateo 1 , Maria del Mar Gutiérrez 1 , Pere Domingo [[dagger]] 2

Keywords:

excess abdominal fat; growth hormone-releasing factor analogue; HIV-1 infection; lipodystrophy; tesamorelin

Lipodystrophy syndrome, which includes diverse forms of anomalous fat distribution and metabolic abnormalities, such as elevated lipid levels, diabetes, high blood pressure and insulin resistance, has become a major problem in patients infected with HIV-1. The problem particularly affects those receiving antiretroviral therapy (ART), with a prevalence of of to 50% in these patients [1-3] .

Morphologic changes, which may include central fat accumulation, peripheral subcutaneous fat loss or a combination of both, can affect a patient's quality of life, negatively impact on ART adherence and limit therapeutic options. In addition, it may translate into an increased cardiovascular risk in these patients [4,5] .

Body shape changes can be difficult to diagnose if only based on patient perception and clinical exam. Several techniques have been used to measure the body fat, such as anthropometry, electrical bioimpedance, dual-energy x-ray absorptiometry (DEXA) scanning, computed tomography (CT), MRI and ultrasonography. The gold standard methods are CT and MRI, but DEXA is the most widely used technique because of its simplicity, safety and low cost, with the limitation that it does not specifically measure visceral fat. However, there are few data on the comparison of these techniques for measuring regional body fat [6] .

Lipohypertrophy may manifest itself by increased abdominal girth as a result of fat accumulation around the abdominal organs as visceral adipose tissue (VAT), enlargement of the neck, dorsocervical fat pad or on the breasts, and other peripheral lipomata. These body changes, especially increase in VAT, have been associated with the metabolic syndrome that leads to increased cardiovascular disease in the general population [7] and increased cardiovascular disease or subclinical atherosclerosis as evaluated by coronary artery calcium imaging in HIV-1-infected patients [8,9] .

Several therapeutic strategies to improve fat accumulation have been evaluated. Several studies have examined the use of growth hormone (GH) owing to its known lipolytic effect and its consequent potential to reduce visceral fat [10,11] . The rationale for its use would be supported by findings that show low concentrations of GH in HIV-1-infected patients with fat redistribution [12,13] . Case studies [14] and longitudinal open-label trials [15,16] indicate that recombinant human GH reduces trunk fat in HIV-1-infected individuals with visceral adiposity. However, GH therapy also reduces subcutaneous fat and is associated with side effects, including deterioration of glucose tolerance, fluid retention, joint swelling and myalgias [17,18] . Other potential disadvantages of its use are its high cost and transient effect, to the extent that discontinuation of treatment results in a nearly complete return to baseline fat levels. Furthermore, a critical question regarding the safety of GH as a lipolytic strategy relates to data suggesting an increased risk of neoplasia. In this setting, IGF-1, a hepatic factor, the secretion of which is stimulated by GH, seems to play an important role [19-21] , potentially owing to the promotion of cell cycle progression and inhibition of apoptosis.

Growth hormone secretagogues, such...

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Gale Document Number: GALE|A244639458