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Title: The metabolic fate of dietary lipid in Human Immunodeficiency Virus : implications for the development of lipodystrophy
Author: Ware, Lisa J.
ISNI:       0000 0001 3563 3658
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2002
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During recent years, a HIV-associated lipodystrophy syndrome similar to Metabolic Syndrome X has been reported in HIV patients using highly active antiretroviral therapy (HAART). While the metabolic processes that appear to be dysregulated are similar to those of Metabolic Syndrome X (hyperlipidaemia and an altered insulin sensitivity), the changes appear to be more profound. While it is possible that HIV-associated lipodystrophy is related to the presence of infection plus genetic and environmental factors such as high saturated fat intakes, obesity, smoking and lack of exercise, there is a clear distinction between this and Metabolic Syndrome X as in HIV-associated lipodystrophy there is concurrent depot specific fat accumulation and fat wasting. This would suggest that use of HAART in HIV infection results in altered adipocyte metabolism. In order to investigate peripheral clearance and uptake of lipid from the circulation, stable isotope labelled fatty acids were given to healthy and HIV subjects with and without HAART and with lipodystrophy associated with specific drug combinations. The results suggest that while HIV infection is associated with delayed clearance of lipid from the circulation, the use of HAART exacerbates this process. In addition, it appears that while PI drugs may delay adipocyte clearance of triglyceride from the circulation, NRTI drugs may reduce adipocyte free fatty acid uptake. An audit of patients with more than six months exposure to HAART (n=545) showed that 25% of patients had elevated plasma lipid, 10% had elevated plasma glucose, but only 9% had both. While this data did not shown an association between specific drug classes and elevated plasma lipid or glucose, there was an association with the duration of therapy. Therefore, it is possible that HAART contributes to the development of HIV-lipodystrophy, but that the cause of this syndrome and the metabolic perturbations are multifactorial.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: HIV