Prevention and treatment

The most straightforward approach to managing mitochondrial toxicity and its associated conditions is discontinuing mitotoxic drugs. Switching from d4T (stavudine, Zerit) or ddI (didanosine, Videx/VidexEC) to other nucleoside reverse transcriptase inhibitors (NRTIs), especially abacavir (Ziagen) or tenofovir (Viread) leads to improvements in lipoatrophy, peripheral neuropathy, pancreatitis, and other side-effects. Most patients can safely restart alternative NRTIs after lactic acidosis resolves or other symptoms improve.^{1 2} It is unclear whether some degree of mitochondrial toxicity is irreversible.

Although damage to the mitochondria improves slowly after the offending drugs are stopped, symptoms can improve quickly.³ Elevated lactate levels typically resolve fairly soon after stopping the offending drug and mitochondrial DNA levels gradually increase.³ Some conditions such as peripheral neuropathy resolve relatively quickly. Lipoatrophy, which typically takes a long time to develop, also resolves very slowly, if at all.^{4 5 6}

Some experts have proposed ‘NRTI-sparing’ regimens that contain only non-nucleoside reverse transcriptase inhibitors and protease inhibitors, but this approach remains experimental. 'Drug holidays' and strategic treatment interruptions are also unproven approaches to preventing or managing side-effects.

Certain nutrients are known to be necessary for proper mitochondrial function and cellular metabolism. The release of damaging free radicals is increased during anaerobic energy production when mitochondria are impaired. This suggests that supplementation of certain nutrients and antioxidants may prove beneficial in managing mitochondrial toxicity.

Several nutritional therapies have been used in an attempt to prevent or treat mitochondrial damage.⁷ There are anecdotal reports and small studies that suggest combinations of thiamine (vitamin B₁), riboflavin (B₂), vitamins C and E, carnitine, and co-enzyme Q10 may stabilise lactate levels and reduce the risk of death in patients with lactic acidosis.^{8 1} Dietary supplements such as selenium, N-acetyl-cysteine (NAC), and alpha-lipoic acid appear to raise levels of glutathione, a major intracellular antioxidant.

Acetyl-L-carnitine, which promotes mitochondrial energy production, reversed the loss of nerve fibres in the skin and reduced neuropathic pain in one small study.⁹ Researchers in London reported that dicholoroacetate appeared to help resolve symptoms in three out of four patients with NRTI-induced acidosis.¹⁰ Finally, German researchers have reported that the supplement mitocnol (NucleomaxX), which is derived from sugar cane and contains uridine, appears to reverse side-effects attributed to NRTI-induced mitochondrial toxicity.^{11 12}