Withdrawal of thymidine analogues from the antiretroviral regimens of patients with clinical signs of lipodystrophy (and replacing it by abacavir or in more recent studies by tenofovir) has been demonstrated to be able to partially revert limb fat loss in a number of studies, including randomized placebo-controlled trials 5-10. Of note, most patients in these studies had stavudine replaced. Carr11 and Martin6 reported an increase in limb fat of 0.39 kg and 1.26 kg 24 and 104 weeks, respectively, after replacing stavudine or zidovudine by abacavir in the Mitox study (the majority of patients was on a stavudine-based regimen at entry, the minority on a ZDV-based regimen). Moyle8 reported an increase of 1.08 kg of limb fat 48 weeks after withdrawal of thymidine analogues. The reported increases in limb fat have been greatest in patients that were pretreated with stavudine compared to patients pretreated with zidovudine. The rate of peripheral fat loss is slower in patients using zidovudine compared to patients using stavudine, suggesting that patients using stavudine may have usually lost more peripheral fat to begin with than patients using zidovudine. Therefore the potential increase in peripheral fat after withdrawal of the thymidine analogue is expected to be greatest in patients using stavudine. The current study, in contrast to earlier studies, will be limited to patients who with respect to thymidine analogue exposure have solely been exposed to zidovudine and never to stavudine. In order to assure that participants in our study have already had the opportunity to lose a reasonable amount of peripheral fat, we will only include patients who have been continuously treated with zidovudine and lamivudine for at least 2 years. Nolan12 reported that treatment-naïve patients receiving zidovudine-based therapy, after 3 years had lost an average of 31% of limb fat compared to baseline12. Patients who continue to use zidovudine appear to continue to progressively loose limb fat at a rate of several percentage-points per year. By limiting our sample to patients who have been treated with zidovudine and lamivudine for over 2 years we can be confident that the average loss of limb fat is large enough to allow for an objectively measurable and statistically significant regain in limb fat to occur after discontinuation of zidovudine and lamivudine.