Nucleoside analogues can induce myopathy or hepatitis by means of mitochondrial dysfunction. We report the case of a 31-year-old man infected with HIV who had a severe lactic acidosis without muscle or liver symptoms. He improved after hemodialysis and withdrawal of antiviral drugs. Muscle and liver evaluation allowed us to ascribe lactic acidosis to a mitochondriopathy induced by zidovudine and didanosine.