65 Lipodystrophy: Fitting the Pieces of the Puzzle Peter Reiss Academic Med Ctr, Amsterdam, The Netherlands

Changes in body fat distribution (lipodystrophy), dyslipidemia and insulin resistance unfortunately are very frequent adverse effects of current combination therapy for HIV-1 infection, and thereby importantly jeopardize the sustained effectiveness of treatment. Both nucleoside analogue reverse transcriptase and protease inhibitors are thought to contribute to the pathogenesis of lipoatrophy in particular, and both drug classes are likely to also be involved in the pathogenesis of lipid changes and insulin resistance both by direct and indirect mechanisms. Of note, neither all protease inhibitors nor all nucleoside analogues are equal with respect to their propensity to induce lipoatrophy and other metabolic complications. Although a number of potential mechanisms which may induce lipoatrophy have been suggested from in vitro studies, including inhibition of fat cell differentiation and mitochondrial toxicity, much remains unclear as to the precise derangements giving rise to aberrrant fat distribution in patients. In particular, why fat wasting does not equally  affect all body fat compartments remains largely unexplained. Although interventions aimed at established fat maldistribution thus far have not proven very effective, the earlier mentioned demonstrated differences between particular antiretrovirals within drug classes have shown promise for establishing combination therapy strategies which are associated with a reduced or at least delayed incidence of lipoatrophy. Given the poorly reversible nature of lipoatrophy it is imperative that such insights be allowed to benefit patients and HIV treatment programmes worldwide.