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Lipodystrophy: Serious Treatment Side Effect

March 2000

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!


Current treatments for HIV/AIDS can cause a range of adverse side effects. In particular, many people on anti-HIV therapy are reporting changes in body shape that are due to the redistribution of body fat and are broadly known as "lipodystrophy." There are two major types of physical changes associated with lipodystrophy: (1)fat wasting, which can include loss of weight in the cheeks, limbs, and buttocks; and (2)fat accumulation,which can include fat deposits on the abdomen, face, and base of the neck (known as "buffalo hump"), other fatty growths (lipomas), and breast enlargement. Other common body changes that may be related to lipodystrophy include early osteoporosis, dry skin, hair loss, menstrual irregularities, and sexual dysfunction, such as decreased libido and impotence.

In addition to physical changes, lipodystrophy affects the body's ability to process and distribute glucose and lipids (fats). Diagnosed through blood tests, these metabolic abnormalities can be very serious:

  • Abnormal glucose metabolism roduces high levels of blood sugar that can cause diabetes. Left untreated, diabetes and the irregular processing of glucose can lead to blindness, kidney failure, and other complications. Luckily, these severe complications are rare.


  • Problems in fat metabolism result in elevated levels of certain lipids such as triglycerides and cholesterol, which heighten the risk of heart attack and stroke. This increased risk of cardiovascular disease is particularly problematic since HIV disease itself is sometimes associated with cardiac abnormalities.

In addition, the importance of preventing the physical changes associated with lipodystrophy should not be taken lightly. Abnormal fat distribution can lead to loss of self-esteem and depression, which are leading causes of non-adherence to the complex and demanding treatment regimens of highly active antiretroviral therapy (HAART). Non-adherence can lessen the effectiveness of HAART and also encourage the development of drug-resistant HIV strains. In addition, as the physical changes that signal lipodystrophy become more widely known,many people may become exposed to the AIDS-related discrimination that can result from a loss of confidentiality regarding one's HIV status.

We still know very little about this disturbing syndrome among people with HIV/AIDS:

There is no accepted definition of lipodystrophy

Doctors do not yet agree on which of the physical and metabolic changes associated with lipodystrophy are most significant or how to precisely measure them. The various symptoms of lipodystrophy are not always linked, and we do not know whether they become more severe over time. Not surprisingly, the lack of a standard case definition has complicated efforts to diagnose and track lipodystrophy, and estimates of its incidence range widely -- from as low as 5% to as high as 78% of long-time survivors of HIV/AIDS.

There is no known cause of lipodystrophy

With no clear definition or uniform diagnostic criteria, it is difficult for scientists to identify the cause of lipodystrophy. Associations have been suggested with various antiretroviral drugs, but no direct causal relationships have been proven.

  • Some researchers have thought that lipodystrophy is a side effect of protease inhibitors, which can disrupt the way normal human cells rocess fat. While it is true that lipodystrophy has become a widespread problem only since the introduction of protease inhibitors, some patients who have never taken these anti-HIV drugs are also experiencing lipodystrophy. And many of the metabolic changes associated with lipodystrophy were observed before the advent of antiretroviral therapy.

  • Other reports suggest that another class of drugs, nucleoside reverse transcriptase inhibitors (NRTIs), may be involved, because they cause toxicities in the mitochondria, which help break down fats.

  • Another theory is that prolonged exposure to high levels of cytokines -- natural hormone-like substances that coordinate healthy immune system functions -- may play a role. It is speculated that when anti-HIV therapy reduces viral load, the corresponding immune system improvement might contribute to the symptoms associated with lipodystrophy.

There is an emerging consensus that the cause of lipodystrophy is multifactorial, and current data support a role for protease inhibitors, NRTIs, and other factors. In fact, what we currently understand as a single syndrome may actually be two or more overlapping syndromes, each with its own causes and needed treatments.

There is no single way to treat lipodystrophy

It is obviously difficult to treat a condition that is poorly defined and for which the cause is unknown. Current remedies focus on specific symptoms of lipodystrophy and include:

  • Exercise and a low-fat diet

  • Conventional treatments for blood abnormalities, including lipid-lowering agents and antidiabetic drugs

  • Changing anti-HIV treatment, e.g., replacing protease inhibitors with non-nucleoside reverse transcriptase inhibitors or switching from one NRTI to another

  • Short-term treatment with human growth hormone, testosterone, or anabolic steroids

It is also important to note that, while lipodystrophy may be linked to antiviral therapy, the benefits of anti-HIV treatment still clearly outweigh the risks for most patients. Virtually all medications have side effects, and the anti-retrovirals implicated in lipodystrophy are extending life for many thousands of people with HIV/AIDS. Ultimately, lipodystrophy may prove to be an unavoidable cost of long-term success with anti-HIV therapy.

So what should individuals experiencing symptoms of lipodystrophy do?

  • Do not stop taking current anti-HIV drugs or make any treatment changes without consulting a doctor.

  • Establish baseline values through blood tests for lipids and glucose and consider taking photographs of your body to enable early detection of any changes in body shape.

  • Have blood sugar and fat monitored regularly.

  • Identify and, if possible, reduce or eliminate other personal risk factors for lipodystrophy, diabetes, stroke, and heart disease, such as smoking and obesity.

Lipodystrophy is now receiving attention from both HIV/AIDS advocates and researchers, and there is good reason to hope that we will soon have a better understanding of this troubling syndrome. The American Foundation for AIDS Research (amfAR) is committed to keeping both people with HIV/AIDS and health care professionals well-informed about lipodystrophy and recently sponsored a series of nationwide community forums that outlined several priorities for further study in this area, including:

  • Clarifying the role of disease progression

  • Determining the contribution of different classes of anti-HIV drugs

  • Identifying more effective treatment strategies

  • Incorporating studies of metabolic changes in clinical trials of HIV/AIDS treatments

  • Considering the impact of metabolic complications during new HIV/AIDS drug development

amfAR continues to support basic biomedical research on HIV/AIDS that may help answer some of these questions. In February 2000, the Foundation released a major new request for proposals in all areas of basic HIV/AIDS research and hopes to fund new projects related to lipodystrophy and other treatment complications.

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by amfAR, The Foundation for AIDS Research. Visit amfAR's website to find out more about their activities and publications.
See Also
An HIVer's Guide to Metabolic Complications
More on Lipodystrophy Treatment