PI Perspective #24

April 1998     View PDF

Protease Paunch or Buffalo Hump

While there have been many reports of lipodystrophy (changes in fat distribution) after long-term protease inhibitor therapy, so far, there are no widely accepted explanations of its cause. “Protease paunch,” once mistakenly called “crix-belly” because people thought it was uniquely caused by indinavir (Crixivan), describes a condition in which body fat is redistributed from other areas and accumulate in hard, fatty layers around the abdomen. One study found that 11% of people developed ‘protease paunch’ or ‘truncal obesity’ and that it was more common in older people and those who were on prolonged antiviral medications. Another study by an Australian group found that lipodystrophy affected up to 64% of people on protease inhibitors. They found a loss of body definition around the face, arms and legs, and a corresponding accumulation of fat around the abdomen and/or behind the neck. This study also noted that the median time to onset of lipodystrophy was about ten months. Additionally, the Australian group noted that a certain portion of the HIV protease enzyme was structurally similar to a naturally occurring enzyme in the body, the role of which is to go around the body and gather up and destroy lipids (fatty substances). They hypothesize that this portion of the protease enzyme may therefore be attracting lipids resulting in lipodystrophy. However, it is not clear why the build up of fat is found around the neck, resulting in a buffalo hump, or around the gut.

The wide differences in the reported frequency of occurrence of lipodystrophy may be attributed to varying definitions of the problem or to differences in how carefully patients and physicians look for it. Most researchers reporting on the problem believe that it is not unique to any particular protease inhibitor. The lead researcher of the Australian study believes that the frequency of occurrence is related primarily to the overall potency of the protease inhibitor regimen, with the greatest risk for people using the most potent dual protease combinations and the least for people using the least potent single protease inhibitor (hard gel capsule saquinavir). No one has reported any solution to the problem other than to stop the use of protease inhibitors, not a very practical suggestion for many people. Some individual physicians anecdotally report achieving some success simply changing the protease regimen, but without a controlled study, it is difficult to interpret this phenomenon. For example, they might simply be changing from a more potent to a less potent regimen. For people who have previously developed resistance to drugs like nevirapine and delavirdine, one possible solution might be to switch to a three-drug combination based on efavirenz and two NARTIs, thus eliminating use of a protease inhibitor. In preliminary studies at least, such a combination appears to equal the potency of most three-drug regimens based on a protease inhibitor.