Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy.
Highly active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome of peripheral fat wasting and central adiposity. HIV-1 protease inhibitors are generally believed to be the causal agents, although the syndrome has also been observed with protease-inhibitor-sparing regimens. Here, we postulate that the mitochondrial toxicity of the nucleoside-analogue reverse-transcriptase inhibitors plays an essential part in the development of this lipodystrophy, similar to the role of mitochondrial defects in the development of multiple symmetrical lipomatosis.
Brinkman
K
K
Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. K.Brinkman@OLVG.nl
Smeitink
J A
JA
Romijn
J A
JA
Reiss
P
P
D019380:Anti-HIV Agents / Q000009:adverse effects*; D004272:DNA, Mitochondrial / Q000187:drug effects; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D015497:HIV-1; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced*; D008069:Lipomatosis, Multiple Symmetrical / Q000139:chemically induced / Q000145:classification; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors