What is lipodystrophy?

• Body fat changes are also known as lipodystrophy.

• Three patterns of body fat changes are being seen in people with HIV: gaining fat on the abdomen (central fat), losing fat from the arms, legs and face, or a mixture of both.

• The causes of body fat changes in people with HIV are still unknown.

• Some people seem more likely to develop some or all of these changes. People who are overweight for their height are more likely to gain central fat. People over 40 are also more likely to gain central fat.

• Fat loss is more common in men than women, although women with average or low body weight are more likely to lose fat than women who are overweight.

• Most research shows that the longer you take HAART, the more likely you are to have changes in your body fat. However, a new study has found that body fat changes usually occur within two years of starting treatment. This suggests that only some individuals are susceptible to body fat changes.

Combination therapy and body fat changes

• At first people with HIV and doctors thought the changes were caused by protease inhibitors. In fact, the changes have also been seen in some people who have never taken protease inhibitors - but not as often.

• Lots of different patterns of body fat changes are being seen, so its likely that different drugs cause different patterns of changes.

• Generally, the protease inhibitors have been linked to fat accumulation while the NRTI class of drugs (AZT, d4T etc) have been linked to fat loss.

• Some - but not all - studies suggest that fat loss is caused by d4T (also known as stavudine or Zerit). For this reason, some doctors now recommend that d4T shouldn't be used for first-line treatment where other options exist.

• Taking a protease inhibitor and NRTIs together resulted in more fat loss than taking an NNRTI like efavirenz with NRTIs, in one major study.

• Ritonavir (Norvir) seems to be the drug most strongly linked to fat gain, when it is used at full dose (600mg twice daily).

Metabolism - the basics

• Metabolism is a general term for the breakdown of food and production of energy within the body. Sugar and fat are sources of energy.

• Abnormalities in sugar and fat levels and in the processing of fats and sugars may indicate metabolic disorders and can cause physical symptoms.

• The general term for blood fats is lipids. There are two main types of lipids: cholesterol and triglycerides.

• Cholesterol comes in two sorts - 'good' and 'bad'.

• 'Good' cholesterol is called HDL and is often reduced in people taking protease inhibitors. HIV infection itself may cause low HDL levels.

• 'Bad' cholesterol is called LDL. A high level of LDL cholesterol and a low level of HDL cholesterol increases your risk of heart disease. Anti-HIV therapy has been associated with high LDL and total cholesterol.

• Certain risk factors increase your risk of heart disease: smoking, high blood pressure, a family history of heart disease and age over 45 years. For people on protease inhibitors, it is especially important to monitor levels of `bad cholesterol (LDL), which causes most of the damage that leads to heart disease. If you have two or more risk factors, the target level for LDL cholesterol is less than 3.4mmol/L.

• The target total cholesterol level is 5.2mmol/L or below. The average cholesterol level in the UK is higher than this (around 5.6mmol/L), and a level of 5.9mmol/L or above is high

• Triglycerides are fats travelling through the bloodstream to be stored in tissues or the liver. The target level is 2.3mmol/L or less, and a level above 4.5mmol/L is considered high.

HIV, combination therapy and abnormal metabolism

• The level of fats in your blood (lipids) may rise when you start treatment with a protease inhibitor treatment. Sometimes they rise far above normal levels and need to be treated by changes in diet, exercise or drugs. An increase to a very high level is especially likely if your levels are already quite high.

• All protease inhibitors increase lipid levels in the majority of people who take them.

• Rises in cholesterol and triglyceride (the two main types of lipids) may put you at higher risk of heart disease, especially if you smoke, you are overweight or you have high blood pressure. Older people are also at higher risk of heart disease when these blood fats, or lipids, go up.

• Your lipid levels should be tested regularly once you start combination therapy, and should be tested before you start treatment to get a baseline. They should be tested first thing in the morning before breakfast to get the most accurate measure: this will show the absolute minimum level. Triglyceride levels also need to be tested after a meal, because they rise very high within an hour or so of eating.

• Very high levels of the triglycerides may cause pancreatitis, a life-threatening illness.

• Changes in the way your body handles sugar (its glucose metabolism) can also occur on protease inhibitor treatment. The most severe change is the development of diabetes, a serious disorder. This has happened in around 1-4% of people in studies, but less serious changes in sugar levels and sugar metabolism also occur. These changes can cause tiredness, poor concentration and loss of strength.

• HIV itself causes high triglycerides in advanced disease. Low HDL or good cholesterol has also been attributed to HIV infection

Treating body fat changes

• At the moment there is no treatment which will reverse all the body fat changes. Some people who stop treatment altogether report improvements, but may not return to normal, and most people with body fat changes are not in a position to stop taking anti-HIV drugs.

• Fat deposits on the abdomen and between the shoulder blades may be reduced by taking human growth hormone, but you have to keep taking human growth hormone for the improvement to last.

• A drug used to treat diabetes, called metformin, may be effective in reducing abdominal fat deposits. It also reduces triglyceride levels and improves glucose metabolism.

• Fat loss from the arms, legs and face may be improved somewhat by switching from d4T to abacavir or AZT.

• A variety of techniques are now being tested to restore the facial appearance of people who have lost fat from the face. The most studied method is injections of polylactic acid (New Fill).

• Neither fat gain nor fat loss has been improved by switching from a protease inhibitor to NNRTI-based regimen, although there is some evidence from one study that switching to abacavir might help. This needs to be confirmed in a bigger study.

• Lipid levels may be improved by switching from a protease inhibitor to an NNRTI or abacavir-containing regimen.

• Both central fat deposits and lipid levels have been improved by a programme of resistance exercise and aerobic exercise. Resistance exercise builds muscles which burn triglycerides, and regular exercise of any sort increases levels of good cholesterol. A brisk walk for half an hour each day reduces the risk of heart disease by one third compared to taking no exercise, according to studies in middle aged women, and this has a similar degree of benefit to aerobic exercise.

• Statins are lipid lowering drugs which have been used successfully to lower lipid levels in people on HIV therapy. The drug used most often is pravastatin.