In this study we therefore aim to demonstrate a small but statistically significant mean increase in peripheral body fat in the patients who switch to emtricitabine and tenofovir disoproxil fumarate as opposed to a further decrease in peripheral fat in the patients who continue the use of zidovudine and lamivudine. Such increases in peripheral fat are not expected to be observable for the treating physicians and the patients themselves. However, the demonstration of even a small sub-clinical effect will provide important information for future patient management with respect to strategies on how to best prevent progressive lipoatrophy. The Mitox study demonstrated that substituting abacavir for stavudine resulted in an increase in limb fat of 390 grams after 24 weeks11. This increase was likewise not noticeable to clinicians and patients, and could only be detected with the use of DEXA scanning. Nevertheless, the results of Mitox had a huge impact on the management of patients: clinicians started to pro-actively substitute other compounds for stavudine, and to exclude stavudine from first-line regimens in order to prevent (progression of) lipoatrophy. If our study would demonstrate a similar increase in peripheral fat in patients substituting emtricitabine plus tenofovir disoproxil fumarate for zidovudine and lamivudine, this could potentially likewise impact on the continued long-term use of ZDV-based regimens. Although the cleanest comparison would be to replace only zidovudine by tenofovir disoproxil fumarate, we also replace lamivudine by emtricitabine. Given that most experts agree that the difference between lamivudine and emtricitabine is probably not very important and emtricitabine has the additional advantage of allowing the possible use of the fixed dose once daily combination of emtricitabine and tenofovir disoproxil fumarate (Truvada®), we have chosen to replace lamivudine by emtricitabine as well.