inPractice® - NRTI Mitochondrial Toxicity and DNA Depletion

Ability of DNA polymerase inhibitors to cause mitochondrial dysfunction initially came to attention during clinical studies of a fluorinated uridine developed to treat chronic HBV infection^{[McKenzie 1995]}
Mitochondrial hypothesis posits that certain NRTIs inhibit mitochondrial DNA polymerase gamma, leading to mitochondrial DNA depletion
Mitochondrial toxicity has been linked clinically to lipoatrophy, as well as several other conditions^{[Brinkman 1998; Kakuda 1999]}