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 li podystrophy syndrome of peripheral fat wasting and central adiposity. HIV-1 protease inhibitors are generally believed to be the causal agents, althou gh the syndrome has also been observed with protease-inhibitor-sparing regi mens. Here, we postulate that the mitochondrial toxicity of the nucleoside- analogue reverse-transcriptase inhibitors plays an essential part in the de velopment of this lipodystrophy, similar to the role of mitochondrial defec ts in the development of multiple symmetrical lipomatosis.