Lactic Acidemia: More Questions than Answers

Early in the development of nucleoside reversetranscriptase inhibitors (NRTIs), a syndrome ofhepatic steatosis and lactic acidosis was recognizedas a rare, but often fatal complication oftherapy. Many of these cases were reported inobese patients, particularly women. The underlyingmechanism of this complication is thought toresult from inhibition of mitochondrial DNA polymerase-gamma activity by NRTIs. MitochondrialATP production is impaired, resulting in cellulardysfunction, evidence of which is readily demonstratedon electron microscopy evaluation of livertissue from afflicted patients.