The thymidine analogues NRTI have been implicated in the pathogenesis of the lipodystrophy syndrome and of peripheral lipoatrophy in particular. Exposure to zidovudine is associated with a slower and possibly lesser degree of limb fat loss than exposure to stavudine. The mechanisms by which thymidine analogue NRTI contribute to lipoatrophy remain uncertain, although there is evidence that drug-induced mitochondrial toxicity at the level of subcutaneous adipose tissue is involved2 3. NRTI are known inhibitors of mitochondrial DNA polymerase gamma and greater degrees of mtDNA depletion in subcutaneous adipose tissue are associated with greater loss of limb fat as measured by DEXA. In addition, NRTI may detrimentally affect mitochondrial function by mechanisms other than mtDNA depletion. It has also been postulated that the normal regional distribution of body fat may be under hypothalamic autonomic neuronal control, and that effects of NRTI on the central and/or peripheral autonomic pathways may be underlying the selective loss of fat in subcutaneous but not in central regions of the body4.