The use of antiretroviral (ARV) medications has been linked to the emergence of severe adverse effects, including mitochondrial toxicity. The liver also appears to be among the affected organs. Nevertheless, different studies suggest that these patients' mitochondrial alterations could be associated to other etiological factors. The goal of this study was to analyze hepatic mitochondria ultrastructural changes in HIV-infected patients under investigation for hepatopathy. Semiquantitative analysis of mitochondria was performed in liver biopsies from 10 patients divided into 2 groups: Group 1 consisted of 5 patients who had never used ARV medications; group 2 consisted of 5 patients who reported previous use of either zidovudine or didanosine. Significant mitochondrial alterations were found in both groups. The summation of the mitochondrial alterations was higher in group 1 ( P < .05) when compared with those who had previously used ARV medications. Therefore, the authors conclude that severe mitochondrial alterations occur in HIV-infected patients who have never been submitted to antiretroviral therapy.