We know that some protease inhibitors cause changes in the body's handling of fats and sugar when they are given to people without HIV. This shows that in HIV-positive people, it is the drugs themselves, and not just the disease or the effects of the drugs on the immune system, which are contributing to the problem.

There is now a lot of evidence that two drugs from the NRTI class, d4T (stavudine, Zerit), and to a lesser extent, AZT (zidovudine, Retrovir) cause fat loss. Because of this it is not recommended that you take d4T or AZT (either by itself or in the combination pills Combivir or Trizivir) as part of your first anti-HIV combination. If you are currently taking either d4T or AZT you should be offered the chance to change to either abacavir (Ziagen) or tenofovir (Viread). Neither of these drugs has been associated with fat loss (in fact, there is evidence that fat loss very slowly improves in people who have switched to them), but they do have other side-effects.

The importance of protease inhibitors to body fat changes is still uncertain. When body fat changes were first noticed in people taking potent combinations of anti-HIV drugs protease inhibitors were initially blamed and studies have shown that protease inhibitors do cause both fat changes. It is hoped that newer protease inhibitors which appear to be less toxic will not cause body fat changes, but it is too early to say for certain that this is the case.It is also possible that particular effects of drugs used in combination therapy could be amplifying a problem which might be caused by the recovery of the immune system from long-term suppression. Similar fat and sugar disturbances and weight gain have been seen in HIV-negative children and young people who received bone marrow transplants and subsequently recovered.