Nucleoside reverse transcriptase inhibitors, mitochondrial DNA and AIDS therapy.

NRTIs are cornerstones of antiretroviral therapy and perhaps the most important drugs developed for AIDS treatment. Judicious use of NRTIs in the fight against HIV infection has afforded significant clinical advances in AIDS treatment. Nonetheless, it is axiomatic to expect side effects from NRTIs as well. A principal toxicity of NRTIs relates to chronic and cumulative MT in various tissues. The long-term impact of this toxicity on affected patients is not clear except in extreme cases where morbidity was severe and mortality occurred. Because of chronicity and potential for severity, NRTI MT remains an important clinical problem. Further studies will help us unravel mechanisms of NRTI MT and the natural history of mitochondrial biogenesis in humans and other mammalian systems.