Mitochondrial toxicity due to antiretroviral therapy (NRTIs)

Nucleoside analogue reverse transcriptase inhibitors (NRTIs) damage mitochondrial function by inhibiting DNA polymerase gamma, which is responsible for the replication of mitochondrial DNA and therefore for the synthesis of mitochondrial enzymes.

These drugs are:

  • zidovudine
  • stavudine
  • abacavir
  • adefovir
  • tenofovir
  • didanosine
  • zalcitabine
  • emtricitabine

NRTI toxicity leading to lactic acidosis

The lactic acidosis is typically profound (studies quote admission lactates of 10-20mmol/L) and long-lasting (as the recovery typically demands the synthesis of new enzymes). Different tissues recover them at different rates; peripheral neuropathy due to NRTIs can last for months after an episode, whereas bone marrow recovers quite rapidly and completely. One can expect that tissues which normally have a high rate of turnover would recover most rapidly.