We report three cases of hepatic steatosis associated with lactic acidosis occurring in HIV positive patients and due to a toxicity of antiviral nucleoside analogues. The clinico-pathological presentation was similar associating digestive signs (vomiting and abdominal pain), polypnea, lactic acidosis, a lethal clinical course, and an hepatomegaly with a diffuse macrovacuolar steatosis. The ultrastructural study performed in two cases showed mitochondrial alterations in hepatocytes. The toxicity of antiviral nucleoside analogues is due to a mitochondrial DNA polymerase inhibition. The incidence of this disease is actually low but probably underestimated. The diagnosis should be rapidly performed and the treatment immediatly interrupted.