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Lipodystrophy and Women

March 2005

Of all the unintended effects from taking anti-HIV therapy, perhaps none is more visible than lipodystrophy. Lipodystrophy can diminish a person's physical and emotional well-being, leading to an increased risk of heart disease, diabetes and depression. This issue of Wise Words explains the many aspects of this condition. The cover article provides a brief overview of lipodystrophy, including a discussion of its effects on women living with HIV.


What Do We Mean by Lipodystrophy?

Lipodystrophy is an umbrella term, covering three separate and possibly related changes in the way our bodies handle fat cells. Lipodystrophy includes both gains and losses in the body's stores of fat and changes in the amount of fat circulating in the blood. Scientists haven't yet agreed on the best way to measure or describe these dysfunctions and predicting who is at most risk for them is difficult.


Fat Gain

lipohypertrophySoon after the introduction of powerful anti-HIV therapy, there was an increase in reports of body shape changes. Abdominal (tummy) fat gain (truncal or central obesity) was among the first complication noticed. The abdominal fat gained is underneath the muscle wall (visceral fat) and feels firm to the touch, as opposed to under the skin (subcutaneous) and soft to the touch. This softer fat is what most people accumulate with typical weight gain.

People also began noticing gains in fat on the back on the neck (buffalo hump or dorsal fat pad), around the neck, and underneath the breasts. The term used by doctors for all these kinds of fat gains is lipohypertrophy. Some people with HIV experienced these body shape changes before the availability of potent anti-HIV therapy, but it was not happening at the rate seen afterwards.


Fat Loss

lipoatrophyWhile some people gained unwanted fat, others lost fat in very specific areas -- most commonly the face, arms, legs and butt. The medical term for this is lipoatrophy and is sometimes called peripheral wasting or facial wasting. This condition has been observed since the early days of HIV and since the very first anti-HIV drugs were used.


Fat in the Blood

Lastly, doctors began noticing increases in the amount of certain fats -- called cholesterol and triglycerides -- circulating in people's blood. This is known as hyperlipidemia or dyslipidemia, and it has been linked to higher rates of heart disease and diabetes-like symptoms. Before the availability and use of anti-HIV drugs, HIV disease progression was associated with decreases in cholesterol levels, particularly "good" cholesterol. An increase in this blood fat is uniquely associated with using certain anti-HIV drugs.


What Causes Lipodystrophy?

At various times, lipodystrophy has been blamed on individual drugs, entire drug classes, and HIV itself. Despite ongoing research, its cause(s) remain uncertain. However, some important observations have been made.

Several studies show a strong link between using protease inhibitors (PIs) and dyslipidemia. Research suggests that some PIs pose more of a risk, most notably ritonavir (Norvir) and Kaletra (lopinavir+ritonavir).

A number of studies have linked nucleoside analogue (NRTI) drugs to lipoatrophy, especially d4T (stavudine, Zerit). Moreover, using NRTIs has been associated with a change in the way cells store and use energy (mitochondria) and with accumulation of fat in the liver.

Although some links have been observed between anti-HIV drugs and symptoms of lipodystrophy, no cause and effect relationship has been established. There are several theories on the root cause of lipodystrophy -- including damage to mitochondria and immune system recovery. Some researchers believe that each of the three dysfunctions described above may have similar but different causes. Until there is better and more convincing research, we cannot know for sure. For more information about mitochondrial toxicity, call Project Inform's Infoline.


What About Lipodystrophy and Women?

Both men and women can experience any of the symptoms of lipodystrophy. Some studies show small differences in the overall rate of lipodystrophy, with women having a somewhat higher risk. Other studies show no difference.

However, women can experience lipodystrophy differently than men. Women seem more likely to experience breast enlargement and overall weight gain. They may be less likely to have facial wasting and higher levels of cholesterol and triglycerides.


Lactic Acidosis and Liver-Related Problems

A relatively rare but serious side effect is the build-up of lactic acid in the body, called lactic acidosis. One result of this is liver problems, including liver enlargement (hepatomegaly) with fat deposits (fatty liver or steatosis). This could result in liver failure and death. Symptoms of lactic acidosis include lab abnormalities, severe nausea, vomiting, and shortness of breath. Although a risk for lactic acidosis and liver problems is associated with all NRTIs, it may be even more of a concern with using specific ones, including d4T and d4T + ddI (didanosine, Videx). People who are overweight and/or those who have used NRTIs for a long time are at greater risk for this side effect. Women, particularly overweight women, appear to have greater risk for this side effect than men. The risk for severe (and possibly fatal) lactic acidosis appears to be greater among pregnant women who are using anti-HIV therapy that includes d4T and ddI.


Why Does Lipodystrophy Matter?

Lipodystrophy can have profound effects on physical well-being. Fat increases can have several effects, from a greater likelihood of diabetes and heart disease to developing sleep disorders, which carry their own health risks. Increases in cholesterol and triglycerides are believed to lead to a higher risk of heart disease. Indeed the research is showing an increased risk of heart disease for people living with HIV, especially those taking anti-HIV drugs.

The emotional impact of lipodystrophy is also critical. Lipodystrophy can change the way our bodies look, including perhaps the most personal and identifiable part of us, our face. These changes can make people feel marked by their disease and can lead to social isolation and depression. This can be particularly hard for people who want to keep their HIV status secret. Fear of lipodystrophy is a common reason for delaying or not taking anti-HIV therapy.

Lipodystrophy remains one of the great mysteries of HIV disease. While important research continues, more is clearly needed. There have been advances in treating fat accumulation (see Human Growth Hormone below), cosmetic treatments for facial wasting, some success with changing therapy, and recent guidelines published for treating dyslipidemia. More research will hopefully lead to further advances toward preventing and treating lipodystrophy.

Checklist for Lipodystrophy

Many people living with HIV are concerned about lipodystrophy. Early changes may be difficult to see. Perhaps the most important thing a person can do is work with his/her doctor to recognize changes in body shape as early as possible. While only a doctor can diagnose you with lipodystrophy, you know your body best and can watch for changes. If you begin to notice changes, consider talking to your doctor. Some things you might pay attention to include changes in how your clothes fit or how your body looks. Some who specialize in diet and nutrition for people with HIV recommend having a friend or family member take a close-up picture of your face and measure your upper and lower arms, thighs and calves about every three months. You can share the pictures and measurements with your doctor and make them a part of your own medical file that you keep at home.

Clothes

  • Do your pants, shorts or skirts fit tighter around the waist?
  • Do your pants, shorts or skirts feel looser in the butt?
  • Do the sleeves of your clothes feel looser?
  • Does the neck of your shirts feel tighter?
  • Has your bra size increased or is it hard to fasten your bra around your ribcage?

Body

  • Are your cheeks the same fullness?
  • Is your waist expanding?
  • Are your butt cheeks the same fullness?
  • Have the veins on your arms become more visible?
  • Are the muscles on your arms and legs more visible?
  • Do you notice any lumps on your arms and legs?
  • Does your neck and upper back look the same size around or thickness?
  • Are your breasts changing? (This may include getting larger, changing shape or feeling what some women describe as "heavier, thicker or different".)


Human Growth Hormone

Human growth hormone (HGH) is also known as somatropin (Serostim). HGH is approved in the U.S. for treating AIDS-related wasting syndrome. HGH is currently being researched in a large study as a way to treat lipodystrophy. It is believed that HGH may help reduce the amount of fat accumulating in the gut, breasts and back of the neck in people with lipohypertrophy. The study also hopes to learn whether low-dose maintenance therapy will keep the fat from returning. HGH is typically used once a day. The drug must be injected under the skin either using a needle or a coiled spring mechanism that injects drug (without a needle) in a pressure stream.


I tried HGH but it eventually made my joints ache and my feet swell.Limitations and Side Effects

Though HGH may prove useful for treating lipohypertrophy, it does not cure it. One side effect is higher glucose (sugar) levels in the blood, which may worsen or increase risk of diabetes. Others include muscle and joint pain, swelling of the hands/feet, and carpal tunnel syndrome (pain, numbness and tingling in the hands/wrists). HGH may also stimulate a tumor to grow. So if you have tumors or cancers that are not under control, HGH should not be used. HGH also increases HIV replication in test tubes, so people taking it should be on effective anti-HIV therapy.


Our Current Situation

It will be some time before early results will be available from this large study. Until then, this use of HGH will remain "off-label". This means that a doctor can write a prescription for HGH, but it is not approved by the FDA for treating lipohypertrophy.

Since HGH is not approved for treating lipohypertrophy, it may be difficult or impossible to get it paid for or reimbursed by insurance or other payment programs. It is very expensive. The high cost and difficulty getting programs to cover HGH makes it a prime target for fraud. You may have seen ads for over-the-counter, "herbal" or "natural" HGH or substances that claim to increase the body's production of HGH. These products are NOT the same as the HGH you get with a doctor's prescription, and many if not all are highly suspect.

If you have lipohypertrophy, you can talk to your healthcare provider about whether HGH may be an option. If you have other questions, call Project Inform's Infoline at 1-800-822-7422.


Treatment Options for Lipodystrophy

Lipoatrophy

There are currently no drugs approved to treat the causes of lipoatrophy. Studies have found that people with lipoatrophy who take a regimen with d4T can reverse fat loss to some degree by swapping it with abacavir (Ziagen). Switching from d4T to tenofovir (Viread) may produce similar results. Because d4T is believed to be a major culprit in lipoatrophy, avoiding it or switching to a viable substitute drug if lipoatrophy is a problem may be a reasonable thing to try.

Sculptra: One Treatment for Facial Wasting

Facial wasting is perhaps the most obvious and apparent form of lipoatrophy. Several products may restore the fullness of a person's face, but only one has been approved for treating HIV-related fat loss in the face. Sculptra (NewFill), approved in the summer of 2004, is a synthetic injectable material known as poly-L-lactic acid. It has been used for years to make dissolvable stitches and different types of implants for cosmetic surgery.

How Does Sculptra Work?

Sculptra is injected below the surface of the skin in the area of fat loss. It causes a gradual increase in skin thickness. Most people need at least four treatments, each about six weeks apart before noticing results. Sculptra doesn't correct the underlying cause of the facial fat loss, but does help improve the appearance by increasing skin thickness in the treated area.

Treatment results differ for each person. In most people studied so far, the results lasted about 18 months. Periodic treatments may be needed to maintain the effect.

The most common side effects include injection-related side effects such as bleeding, tenderness or pain, redness, bruising, or swelling. Also, small bumps under the skin in the treated area can form a number of weeks after treatment. The bumps are usually not visible, but can sometimes be felt under the skin.

Sculptra, made by Dermik Aesthetics, is only available through doctors who have been authorized by the company to use it. It costs roughly $980 per treatment for the Sculptra, plus another $350-$500 to the doctor performing the injections. For people who cannot afford Sculptra, but who need treatment, Dermik Aesthetics has a Patient Assistance Program (PAP). To find a doctor near you or to find out more about the Sculptra PAP, call their toll-free number at 1-888-728-5787.

What About the Arms and Legs?

For some people the loss of fat in the legs and arms can be as disturbing as facial wasting. When the fat is lost over time, the veins and muscles in the arms and legs become much more defined and obvious. Because most women carry more fat in their limbs than men, it sometimes takes longer for this kind of wasting to occur. When it does, however, it can often be much more obvious in women. There aren't yet any treatments, but it is hoped that current studies about lipoatrophy will yield promising treatments for the condition.

What About the Butt?

Another area of fat loss common with lipoatrophy is the butt. Loss of fat in the butt may not only affect the way a person feels about their appearance and change the way clothing fits, but it can also be physically painful. If enough fat is lost around the hips and tailbone, this can make sitting for any length of time quite uncomfortable.

There has been far less research on different methods for restoring fat loss in the butt than for the face, but at least three forms of experimental procedures are being tried. None described here would be covered by insurance, so someone interested in them would have to pay out of pocket. The procedures include fat transfer, silicone implants, and injections of a substance called polyalkylimide (Bio-Alcamid). Though used in some European clinics to treat facial wasting, Bio-Alcamid is not currently approved for use in the U.S. More research is needed to determine how effectively it can treat wasting in the butt.

Fat transfer has not proven to be a very successful way to restore fullness in any part of the body. The results are too unpredictable and no method used so far has resulted in lasting results for most people who try it. It is also fairly expensive. Since people with lipoatrophy have few areas from which to take the fat, it is unlikely to be explored seriously.

It isn't clear whether silicone implant surgery will be either safe or effective for people with lipoatrophy. Several aspects of this surgery can make it less useful for treating wasting in the butt. First, the implant goes underneath the muscle, rather than on top of it, just under the skin where the fat used to be. The implant is also solid, rather than the kind of soft fluid sacs used as breast implants. Lastly, the recovery time is usually longer and more painful than almost any other form of plastic surgery and can cost more than $7,000.

Lipohypertrophy

The accumulation of fat around the abdomen, breasts and neck (called lipohypertrophy) is a significant and visible problem for people living with HIV.

Liposuction

Liposuction is the physical removal of fat tissue, using a vacuum-like device. Liposuction has proven successful for some people with lipohypertrophy, but not others.

In the case of abdominal fat accumulation, liposuction is not generally feasible. Unlike normal fat accumulation which consists of fat underneath the skin, in lipohypertrophy the fat is under the muscle wall, around the internal organs. This makes liposuction dangerous and likely impossible.

In the case of fat pads on the back of and around the neck, there are two complications. The first is this fat often has fibrous tissue mixed in, which can interfere with liposuction. Second, there have been numerous reports of the fat returning after removal. Some have reported better success using ultrasound technology to assist with liposuction. Despite these challenges, there has been some success. Any liposuction will cause pain, tenderness and possibly bruising and scarring where the vacuum is inserted.

Breast Reduction Surgery

Breast reduction surgery is more invasive than liposuction and involves cutting out fat and breast tissue, reshaping the breast, and moving the nipple. While people are often up and about in just a few days, pain persists for several weeks and physical activity is restricted. Breast reduction surgery is much more painful than breast implants. Some report more enlargement occurring even after breast reduction surgery. Many have run into difficulties in getting this surgery covered by insurance. This is because the surgery is sometimes deemed cosmetic rather than medically necessary.

Drug Treatments

There are few good data on using drug treatments to reverse fat accumulation. Most research has been done on using anabolics (drugs that build muscle) like testosterone, oxandralone, and human growth hormone (HGH). Many anabolics have "masculinizing" side effects. For women, these can include darker and coarser hair growth on the face, balding, and changes to the timing and flow of their periods. Oxandralone and HGH do not have this problem. One small study of low-dose HGH showed some promise in reversing fat accumulation. A larger, follow-up study is currently underway. (See Human Growth Hormone, above.)

Hyperlipidemia

Increases in the amount of certain fats, called cholesterol and triglycerides, circulating in the blood is called hyperlipidemia. Hyperlipidemia is a problem for many people living with HIV who are taking or have taken anti-HIV drugs. Mounting evidence suggests that this increase in blood fats puts people at an increased risk of heart disease.

What to Do: Prevention

Heart disease is one of the most common health problems in America. Small studies suggest that diet and exercise counseling made little to no impact on hyperlipidemia associated with using anti-HIV drugs. Although no impact was seen on lipid levels in these studies healthy living may still have decreased risks for heart disease in some meaningful yet unmeasured way.

What to Do: Treatment

The most common drugs used to treat high cholesterol levels are called statins. Pravastatin (Pravachol) or atorvastatin (Lipitor) are often used when changes in diet and exercise haven't controlled the problem. Fluvistatin (Lescol) may also be an option, although there aren't as much data on its use. Also, some statin drugs and anti-HIV drugs can't be taken together. Niacin is often used to treat high cholesterol, but it has been linked to insulin resistance (a risk for diabetes) and flushing of the skin. Niacin should be used with caution.

Drugs called fibrates are used for elevated triglycerides (again when diet and exercise alone haven't been enough). Gemfibrozil (Lopid) or fenofibrate (Tricor) are preferred options. Some research has shown that omega-3 fatty acids -- found in fish oils, flax seeds and leafy green vegetables like kale -- can reduce triglycerides as well.

For people with both elevated cholesterol and triglycerides, there are few data to help guide people making treatment decisions. Several small studies of people living with HIV using both a statin and a fibrate have shown them to be safe. However, there's a concern about an increased risk for damage to muscle tissue over time, called myopathy. Some propose that adding niacin to statin therapy might be a safer alternative, but they caution that people need to be carefully checked for signs of insulin resistance.

What About Diet and Exercise?

JoggingA balanced diet and regular exercise are important parts of healthy living. What do we know about their roles in preventing and treating lipodystrophy?

Lipoatrophy:
Diet and exercise have not been shown to help restore fat lost to lipoatrophy.
Lipohypertrophy:
Some studies show modest improvement in lipohypertrophy from changes in diet and exercise, while others show none.
Hyperlipidemia:
Regular exercise and a diet low in saturated and trans fats can help control hyperlipidemia and reduce a person's risk of heart disease.


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