Impact of mitochondrial toxicity of HIV-1 antiretroviral drugs on lipodystrophy and metabolic dysregulation.
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 HIV-associated lipodystrophy (HIVLD) as a model of clinical MtT we discuss management strategies and the potential for these toxicities to impact on future ARV development.
Feeney
Eoin R
ER
School of Medicine and Medical Sciences, University College Dublin, C339 Health Sciences Building, Dublin 4, Ireland. eoin.feeney@ucd.ie
Mallon
Patrick W G
PW
D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors