While a substantial number of clinicians and researchers seem convinced that lipodystrophy is a new phenomenon related to PI treatment and is associated with hyperinsulinemia, hypertriglyceridemia, and hypercholesterolemia, Kotler and associates disagree. They argue that alterations in fat distribution are simply a part of HIV infection and that increased abdominal fat deposition -- "protease paunch" and "crixbelly" -- preceded the introduction of PIs. Dr. Kotler's group compared the body composition and fat distribution of patients who had been on PIs with patients who had never received PIs and with healthy controls. They found no significant difference in those parameters and concluded that alterations in body fat distribution preceded the introduction of (and are unrelated to) PIs, and that those changes are most likely related to the stage of HIV disease and viral burden.

Regardless of whether lipodystrophy is PI-related, it is extremely disturbing to patients. Studies are in progress to determine whether this syndrome is related to PIs or whether it is just another problem related to HIV infection itself. Meanwhile, many patients will be seeking some relief from this syndrome. Unfortunately, at this point, treatment options for lipodystrophy are somewhat limited and uncertain. My clinical experience and some preliminary studies indicate that lipodystrophy syndrome is generally self-limited and that some patients experience a remission of symptoms over time, even if they continue with the same antiretroviral regimen.  Lipid abnormalities should of course be corrected, and gemfibrozil and atorvastatin may be effective in that regard.

There are some reports of remission of lipodystrophy with recombinant human growth hormone, and a clinical trial is under way.  Finally, given the possibility that lipodystrophy is PI-related and that the consequences of long-term PI therapy are unknown, consideration should be given to PI-sparing regimens, especially in patients with high CD4+ cell counts and low viral loads.