Pathogenesis of HIV Lipodystrophy

Our understanding of the pathogenic mechanisms underlying HIV lipodystrophy has evolved since the initial suggestion that HIV lipodystrophy was a simple and direct consequence of protease inhibitor induced drug toxicity. The complex nature of the syndrome and the multiple factors seemingly associated with the development of this syndrome have led some investigators to consider HIV lipodystrophy as a multi-factorial disease that may be more than one syndrome. Rather, HIV lipodystrophy might more appropriately be viewed as a syndrome caused by overlapping drug toxicities of both the nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) classes of anti-retro viral medications in conjunction with host factors. The toxicity is increased by combined use of these two classes of medications, and the manifestation of toxicity may be strongly influenced by various modifying factors such as immunosupression, age, race, and hormonal status. Whether the lipodystrophic effects are mediated completely by direct medication toxicity or whether the ultimate result is partially mediated by complex host-viral interaction remains to be elucidated.