Lactic acidosis and multiorgan failure secondary to antiretroviral treatments in HIV-infected patients

A serious complication: Antiretroviral therapy may induce severe lactic acidosis with multiorgan failure in HIV-infected patients. Clinical description: Patients are admitted for onset of dyspnea, abdominal pain, nausea, vomiting or diarrhea, with weight loss and general fatigue over the past few days. Physical findings are usually not contributive except for constant presence of hepatomegaly. Laboratory examinations reveal severe metabolic acidosis with increased anion gap and serum lactate elevation. Perturbations of hepatic and pancreatic enzyme values may exist. Echotomography and CT scan demonstrate fatty liver, confirmed by histological examination of the biopsy. Outcome in the intensive care unit is generally multiorgan failure and death. Symptomatic treatments, mechanical ventilation, bicarbonate infusion or hemodialysis appear to be ineffective in most severe cases. Pathophysiology: Antiretroviral nucleoside analogs are inhibitors of mitochondrial DNA polymerase gamma. This explains the dysfunction of the mitochondrial respiratory chain, leading to inhibition of lactate metabolism in the liver and enhancement of serum lactate and acetone body levels. Elevation of lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios suggest mitochondrial dysfunction. Many other co-factors may be associated. Therapeutic approach: Several therapeutic strategies (thiamine, coenzyme<Aucun> Q, carnitine and riboflavin) have been tried. They rely on the pathophysiological hypothesis that sustained cellular dysfunctions cause this clinical syndrome.