Lipodystrophy and HIV treatment


Key points

  • Lipodystrophy is a side-effect of some anti-HIV drugs. These are mainly older drugs which are now rarely used.
  • Lipodystrophy may include an accumulation of fat, a loss of fat, or both.
  • It is common for people who have lipodystrophy to have metabolic disorders such as high blood fats.

Lipodystrophy refers to abnormal changes in the way fat is distributed around the body, along with resulting metabolic complications. Loss of fat from an area is called lipoatrophy, while the accumulation of fat is termed lipohypertrophy. In people with lipodystrophy, either or both of these processes can occur.

Metabolic complications can include high levels of fats and sugars in the blood that could lead to the development of other conditions, such as heart disease and diabetes.

Lipodystrophy has been seen in people living with HIV taking older antiretroviral drugs – particularly stavudine (d4T, Zerit), zidovudine (AZT, Retrovir), didanosine (ddI, Videx) and indinavir (Crixivan). These drugs are no longer widely prescribed.

The drugs most widely used in HIV treatment today are not thought to cause lipodystrophy. New cases of lipodystrophy from more recent medications rarely occur.

Various changes have been seen in people living with HIV affected by lipodystrophy:

  • Accumulation of fat: increased waist size (without rolls of fat), increased breast size, fat gain around the back of the neck and upper back, fat gain around the neck and jaw. Fat may also accumulate in or around the organs (such as the liver) and in the muscles.
  • Loss of fat: facial wasting, especially of the cheeks, buttocks, and limbs. This results in prominent veins in the arms and legs due to fat loss.

When fat is lost, it is fat from under the skin (subcutaneous fat) that is affected. The abdominal fat gain in lipodystrophy is made up of visceral fat which accumulates around the internal organs, causing the belly to feel taut and pushed out. This is different to the squeezable fat gained if people put on weight through over-eating or lack of exercise, as happens in obesity. Compared to people with generalised obesity, there is relatively more visceral fat and less subcutaneous fat in people with HIV who have lipodystrophy.

What causes lipodystrophy?

Lipodystrophy refers to different signs and symptoms in people living with HIV and is not one syndrome with a single cause.

The mechanisms underlying lipodystrophy development in HIV-positive people are only partially understood. Exposure to specific antiretroviral medications is likely important in the development of lipodystrophy.

Research has shown that the loss of fat in particular may be caused when mitochondria ­­– responsible for producing energy for your body’s cells ­­– are damaged or decline in number as a result of older medications, such as stavudine and zidovudine. This is known as mitochondrial toxicity.

Fat accumulation is not as well understood but has often also been seen in people on the same medications. Increased visceral fat tissue appears to be associated with metabolic disorders.

Other factors related to the individual’s health and specifically to HIV may also play a role in the development of lipodystrophy. These include duration of HIV therapy, duration of HIV infection, extent of damage to the immune system when HIV therapy was commenced, gender, age, family history, diet, and body mass and fat prior to treatment. However, none of these have been proven to cause lipodystrophy.

Effects on overall health

Body fat changes may be stigmatising, and research has shown that they are a potential source of stress and worry amongst people taking HIV treatment. This may lead to decreased quality of life and emotional wellbeing in people living with lipodystrophy.

The metabolic complications associated with lipodystrophy may have a negative impact on health. These complications include insulin resistance (an inability to respond to insulin, which is necessary for processing sugar), high cholesterol and high triglycerides (fats). Insulin resistance may result in diabetes, while high levels of fat in the blood are associated with heart disease, stroke and pancreatitis. Visceral fat can also appear in places such as the liver, leading to inflammation, fatty liver disease and cirrhosis.

Any risk is likely to be highest in people with other risk factors such as high blood pressure, diabetes, obesity, smoking, or a family history of heart disease.

You'll have regular blood tests to monitor levels of fats and sugars in your blood at your HIV clinic. This helps with the management of any metabolic complications. You can lower the risk of heart disease and diabetes with exercise, a balanced diet, losing weight if you are overweight, and by stopping smoking.

Treatments for lipodystrophy

There is no cure for lipodystrophy and research suggests that changes in body fat distribution caused by the use of older medications may be irreversible. If you are still taking one of the medications associated with lipodystrophy, switching to another medication will help prevent further lipodystrophy.

The management of lipodystrophy is focused on managing metabolic complications and treatments to improve cosmetic appearance. Diet and exercise are an integral part of management.

"The management of lipodystrophy is focused on managing metabolic complications and treatments to improve cosmetic appearance. "

Conventional therapies, including metformin and insulin, are used to treat diabetes and lipid-lowering drugs (statins) are used to manage lipid levels to prevent heart disease. Some statins can interact with some HIV drugs, so your doctor will choose your drugs with care and monitor you closely. Regular exercise (a combination of resistance and cardiovascular activities), a balanced diet with lots of vegetables and wholegrains, and stopping smoking can all help reduce your risk of heart disease.

Fat loss from the face can be repaired in a number of ways. The most commonly used technique involves filler injections (such as Sculptra or Radiesse) into the affected areas. This treatment is often available from HIV clinics so ask your doctor or another member of your healthcare team if this treatment is available to you.

Surgery can be an option for removing fat accumulation around the neck. However, there may be poor outcomes when using liposuction as fat deposits may return. Other possible treatments for fat accumulation involve human growth hormone or anabolic steroids. Again, you can talk to your doctor about these.

Low-resource settings

Lipodystrophy continues to affect many people in low and middle-income countries, as the antiretroviral medications linked to lipodystrophy, particularly lipoatrophy, were still widely used up until a few years ago. Despite the World Health Organization recommendation to discontinue stavudine use in 2010, the low cost and simplicity of the drug led to it taking several years for African countries to phase out its use.

This has considerable implications for the risk of metabolic diseases, quality of life and adherence.

In these countries, extremes of both obesity and malnutrition may be present, exacerbating the effects of lipodystrophy for HIV-positive people.

Management of lipodystrophy in low-resource settings includes lifestyle modifications (diet and exercise), lowering the dosage of older medications or ideally, switching to a newer antiretroviral medication.

Next review date

Thanks to Alastair Duncan for his advice.