AIDS Treatment Update, Issue 64, April 1998
Keith Alcorn

Lipodystrophy involves the loss of the thin layer of fat under the skin, making veins seem to protrude; wasting of the face and limbs; and the accumulation of fat on the abdomen (both under the skin and within the body cavity) or between the shoulder blades. Women may also experience narrowing of the hips and enlargement of the breasts.

HOW COMMON IS IT?

Cases of lipodystrophy have now been reported among people taking any of the four licensed protease inhibitors. Although lipodystrophy's early nickname was `Crix belly' (after Crixivan, the brand-name of indinavir), it is now clear that it is not specific to indinavir.

Estimates of the proportion of people who develop lipodystrophy during PI therapy ranged from 11% to 64% in different studies, not least because some researchers only reported cases in which body changes were physically apparent, while others used scans to measure very subtle body changes.

Many people on PIs are experiencing increases in blood cholesterol and triglycerides (fats which can contribute towards heart disease if present at high levels for long periods). No-one yet knows if these are related to lipodystrophy or are an entirely separate side-effect, nor what the longer term implications may be.

In one study five out of 72 PI recipients had developed what researchers called `protease paunch'. These individuals' average age was 46, higher than the average of the group as a whole, so the researchers suggested that age might increase the risk (abstract 408).

The strongest predictors of developing `protease paunch', according to those researchers who had identified enough cases to reach meaningful conclusions, were the duration of protease inhibitor treatment, and the use of a dual PI combination rather than one PI alone. In an Australian trial of the ritonavir/saquinavir combination, 30% of participants had developed lipodystrophy after 48 weeks treatment, 68% had elevated cholesterol, and 85% had elevated triglycerides (abstract 390).

Another Australian study showed that people with lipodystrophy (as diagnosed by body scans rather than just physical examination) were significantly more likely to have elevated triglycerides, cholesterol and insulin levels. They also found that lipodystrophy developed more quickly, and was more noticeable, in people on ritonavir/saquinavir (abstract 410).

In 11% of participants in the Canadian trial of ritonavir/saquinavir, triglyceride levels increased three- to four-fold during treatment. Some were treated with drugs that reduce the level of lipids (fats that circulate in the blood); gemfibrozil (Lopid) and clofibrate reduced lipid levels by more than 50% in four out of six cases (abstract 388).

Dr Ian Williams of the Mortimer Market Centre commented "It would be very useful to know whether there's a relationship between elevated cholesterol and triglycerides and lipodystrophy, whether they are a kind of surrogate marker for subsequent changes in weight, and whether reducing lipid levels reduces the future risk of lipodystrophy".

Some doctors stress that while lipodystrophy is "cosmetically unfortunate" - and this in itself may cause significant psychological distress - it remains to be seen whether it is a symptom of a serious underlying condition.

WHAT CAUSES LIPODYSTROPHY?

Australian researchers suggested that protease inhibitors might cause lipodystrophy by interfering with a liver protein which is supposed to mop up fat in the circulation, and which strongly resembles an area of HIV's protease gene (abstract 410). Since all protease inhibitors currently in use are structurally similar, they may all have some effect on this liver enzyme, although genetic and biochemical differences between individuals will play a part too.

However, one expert on nutritional aspects of AIDS recently suggested that lipodystrophy may not be a direct side-effect of protease inhibitors at all. Dr Donald Kotler has reported several cases of the syndrome among people who have never taken a protease inhibitor, and suggests that occasional cases of altered fat distribution have been seen since the early days of the epidemic. His article is available on the Internet at http://www.healthcg.com/hiv/updates/feb98/

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