By the end of 1998, doctors around the world had began to collect reports of strange changes in body shape, blood fats and hormones in their patients on HAART. Collectively, they called these side effects the "HIV lipodystrophy syndrome." While there is not consensus about a definition for the syndrome, features that have been associated with lipodystrophy can include the following:

Changes in body fat

• Loss of fat (fat wasting) just under the skin (subcutaneous fat), particularly in the face, arms and legs. This results in sunken cheeks and more prominent veins in the arms and legs.
• Fat gain or accumulation, mainly deep in the belly and in the breasts (mostly in women). Note that sometimes breast enlargement is due to breast tissue (glands, ducts) that grows inappropriately. Although fat gain is a common feature of lipodystrophy, buffalo humps are not. Sometimes small lumps of fat appear on the abdomen or back.

Changes in insulin and blood sugar

• The hormone insulin helps to maintain blood sugar levels within a normal range by allowing cells to take in sugar (glucose). In PHAs with lipodystrophy, higher-than-normal levels of blood sugar can occur. This problem arises because insulin does not have the same effect that it used to — cells have become less sensitive to this hormone's action. This state is called "insulin resistance." To compensate for reduced sensitivity to insulin, the body pumps more of this hormone into the blood. Not surprisingly, some PHAs with lipodystrophy have higher-than-normal levels of insulin. Over time, serious cases of insulin resistance can lead to diabetes.

Lipids — cholesterol and triglycerides

• Another common feature seen in lipodystrophy is higher-than-normal levels of cholesterol and triglycerides. Prolonged elevation of lipid levels — a condition called "dyslipidemia" — increases the risk of cardiovascular disease and diabetes. Poor dietary habits, tobacco smoking and lack of regular exercise also increase this risk.

While we have listed three groups of side effects associated with lipodystrophy, it is important to remember that not all of them occur at the same time in the same person. For instance, some people may have fat accumulation without fat loss, or vice versa. Moreover, if caught early on, insulin resistance and high lipid levels may, in some cases, be managed — depending on the severity of the side effect — with a number of interventions, including improvement in diet, use of certain supplements, exercise and various lipid-lowering drugs.

Exactly why these side effects occur is not clear. However, what is clear is that lipodystrophy was not reported before 1996 and it is probably caused by the following factors:

• drugs used to treat HIV
• the body's response to these drugs

In this issue of TreatmentUpdate, we review recent findings that may help explain some aspects of the lipodystrophy syndrome. CATIE has recently published A Practical Guide to HIV Drug Side Effects, which is chock-full of many helpful hints and suggestions for dealing with drug-related side effects. It is available in print or on our website at www.catie.ca.

REFERENCES

1. Chen D, Misra A and Garg A. Lipodystrophy in human immunodeficiency virus-infected patients. Journal of Clinical Endocrinology and Metabolism 2002 Nov;87(11):4845-56.

2. Behrens GMN, Boerner A-R, Weber K, et al. Impaired glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy. Journal of Clinical Investigation 2002 Nov; 110(9):1319-1327.

3. Bastard J-P, Caron M, Vidal H, et al. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet 2002 Mar 23;359(9311):1026-31.

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