NRTI-Associated Mitochondrial Toxicity

Some of the toxicity associated with antiretroviral therapy appears to be linked to the use of NRTIs and bears a notable resemblance to genetically based mitochondrial diseases. Given this similarity, could acquired mitochondrial dysfunction -- either caused or accelerated by NRTI use -- account for such seemingly unrelated antiretroviral toxicities as neuropathy, myopathy, hepatic steatosis, lactic acidosis, bone marrow suppression, and fat atrophy? In this review, we will explore the scientific basis for NRTI-related mitochondrial toxicity, its clinical manifestations, and proposed therapies.

Potent combination antiretroviral therapy has resulted in sharp declines in HIV-related morbidity and mortality -- advances that have, however, come at the cost of significant drug-related toxicities. Much attention has been focused on the HIV lipodystrophy syndrome, which can include peripheral fat wasting, central adiposity, insulin resistance, and hyperlipidemia. PIs may play a major role in some aspects of this syndrome, most notably insulin resistance and hyperlipidemia. However, some of the toxicity associated with antiretroviral therapy appears to be linked to the use of NRTIs and bears a notable resemblance to genetically based mitochondrial diseases. Given this similarity, could acquired mitochondrial dysfunction -- either caused o…

Authors

Raphael J. Landovitz, MD

Paul E. Sax, MD

NRTI-Associated Mitochondrial Toxicity

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Authors