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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Impact of Mitochondrial Toxicity of HIV-1 Antiretroviral Drugs on Lipodystrophy and Metabolic Dysregulation

Author(s): Feeney Eoin R. and Mallon Patrick W.G.

Volume 16, Issue 30, 2010

Page: [3339 - 3351] Pages: 13

DOI: 10.2174/138161210793563482

Price: $65

Abstract

Nucleoside reverse transcriptase inhibitors (NRTIs) are components of most current antiretroviral (ARV) regimens. Side effects arising from mitochondrial toxicity (MtT) induced by these drugs is a common reason why patients treated with NRTI change or discontinue therapy. These toxicities can be difficult to reverse, and on occasion can be life-threatening. The exact pathogenesis underlying NRTI-induced mitochondrial toxicity remains unclear, and likely differs for specific NRTI drugs. We review mitochondrial physiology, what is known about how NRTI cause MtT, and what areas of pathophysiology remain unclear. Using the example of HIVassociated lipodystrophy (HIVLD) as a model of clinical MtT we discuss management strategies and the potential for these toxicities to impact on future ARV development.

Keywords: Mitochondrial toxicity, HIV, NRTI, mtDNA, mtRNA, HIV-associated lipodystrophy


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