It has been suggested that lipoatrophy associated with exposure to nucleoside analogues is caused by depletion of mitochondrial DNA (mtDNA). The aim of the present study was to determine whether switching treatment from a thymidine analogue to abacavir was associated with an increase in the mtDNA copy number in peripheral blood mononuclear cells (PBMCs). Of 111 patients with lipoatrophy who were randomized to have treatment switched to abacavir or to continue treatment with thymidine analogues, 94 patients had PBMCs obtained at baseline and at weeks 4, 12, and 24, for quantification of the mtDNA copy number. During the 24-week study, there was no significant change in mtDNA copy numbers in PBMCs in either treatment group, despite improvement in peripheral lipoatrophy among patients whose treatment was switched to abacavir.