BioDrugs. 2000 Aug;14(2):83-91. doi: 10.2165/00063030-200014020-00002.
Potential of recombinant human growth hormone in HIV-associated adipose redistribution syndrome.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
R A Torres, J A Cadman
PMID: 18034560
DOI: 10.2165/00063030-200014020-00002
Abstract
HIV infection recently has been complicated by the emergence of a rare metabolic dysmorphic disorder characterised by fat atrophy, redistribution and accumulation in the setting of hyperlipidaemia and, on occasion, hyperglycaemia. The disorder, sometimes referred to as HIV-associated Adipose Redistribution Syndrome (HARS), has a prevalence rate of about 50 to 60% and seems temporally related to the advent of highly active antiretroviral therapy, especially the usage of protease inhibitors. Various studies also implicate the nucleoside analogues stavudine, didanosine and lamivudine in the pathogenesis of HARS, especially fat atrophy. It is uncertain whether the changes described in HARS represent a single syndrome or a group of related syndromes. Reports have noted differences between morphologic and metabolic changes. More recently, it has been suggested that fat atrophy and fat accumulation may also be separate entities. There are several potential pathogenic theories for HARS that implicate both protease inhibitors and nucleoside analogues as causative agents. However, long term HIV infection rather than any specific agent or class of agent may be the source. Recombinant human growth hormone (rhGH) is a mammalian cell-derived product, which has been useful in a variety of human disorders ranging from pituitary dwarfism to septic shock. It has anabolic, immunological and metabolic properties that restore normal functioning to many aberrant disease pathways. The lipolytic properties of rhGH have been especially beneficial in the diminution of localised fat accumulation in the dorsocervical area (buffalo humps) and truncal region. This has been observed in various reports where rhGH has been administered at doses of 5 to 6 mg/day in patients with HARS for periods ranging from 3 months to >2 years. Relapses after discontinuation of rhGH occurred in most patients. Adverse effects included carpal tunnel syndrome, facial swelling, arthralgias and myalgias and worsening or onset of hyperglycaemia. The small uncontrolled studies conducted to date suggest that the most notable effect of rhGH treatment is the reduction of truncal adiposity and buffalo humps and that the agent has little effect on restoring the adiposity of the appendicular muscles, buttocks or face. Although most patients with HARS have associated hyperlipidaemia, rhGH has no notable effect on serum cholesterol and triglyceride levels. However, blood glucose levels can increase and pre-existent diabetes mellitus may worsen. A short term confirmatory placebo-controlled trial in patients with HARS is urgently needed, as are comparative trials using other anabolic agents such as oxandrolone and testosterone.
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