The Etiology of Metabolic and Morphological changes During Antiretroviral Therapy: Many Small Pieces in a Large Jigsaw

The etiology of fat distribution, lipid and glucose handling abnormalities remains obscure. Current hypotheses regarding the roles of both protease inhibitor and nucleoside analogues are not supported by evidence. In particular, the syndrome has been observed in individuals naïve to protease inhibitors and naïve to nucleoside analogues. Non-drug associations observed in cross-sectional studies, such as age, genetic characteristics, changes in CD4 and viral load with therapy, and alterations in hormonal and cytokine profiles during therapy suggest that the drugs alone are not the cause. Indeed, observations in other disease areas suggest metabolic and possibly morphological abnormalities may often accompany recovery from immune deficiency or immunosuppression. In the absence of understanding of the ætiology, treatment remains challenging. Evidence regarding drug switching suggests modest benefits can be gained with regards to metabolic and fat accumulation aspects in some patients with the removal of protease inhibitors from the regimen. Nucleoside analogue switching has not been evaluated thus far in controlled trials but available evidence suggests no differences exist in first-line regimen use between zidovudine and stavudine for the risk of dyslipidaemia or morphological changes. Treatment therefore currently consists of manifestation specific management together with dietary advice and exercise.