Management of Bone Disease and Body Composition Changes

  • Author: Donald P. Kotler, MD (More Info)
  • Section Editor: Eric S. Daar, MD
  • Editors in Chief: Daniel R. Kuritzkes, MD; Joseph J. Eron, Jr., MD
  • Last Reviewed: 5/7/18 (What's New)


  • 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]

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