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Body Distortion -- Lipodystrophy

Part of A Practical Guide to HIV Drug Side Effects

2006

Lipodystrophy (lipid = fat; dystrophy = disorder)
Lipodystrophy syndrome is the term used to describe a range of symptoms that include changes in body shape and metabolic changes (for the latter, see "Cardiac Concerns" and "Insulin Resistance and Diabetes"). Lipodystrophy-associated body changes -- loss of fat in the face, arms, buttocks and legs, and, at the other extreme, enlarged breasts and bellies, along with buffalo humps (fat at the base of the neck) and fatty tumours (lipomas) -- are at the top of many PHAs' don't-want-to-have-it lists. The causes are not yet fully understood but many think that they may include some combination of drug side effects, changes in the body that occur when HAART leads to immune restoration, HIV disease itself, and possibly other factors that are as yet unknown. Unfortunately, discontinuing medications doesn't always reverse the problems, although there have been reports of gradual improvements over time in at least some people.

Although many people think of this as a "cosmetic" issue, it certainly isn't when:

  • the buffalo hump creates difficulty sleeping, headaches and neck pain, which may obstruct side vision
  • the abdominal fat causes difficulty breathing, digestive problems and back pain
  • the facial fat loss and overall body distortion cause serious emotional distress (involved in the development of anxiety and depression), an unwillingness to pursue life activities and non-adherence to medications

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Research is underway to attempt to determine exactly why lipodystrophy occurs and how to prevent or treat it so in the future there may be much better solutions. For now, therapies differ depending on the area affected and whether the problem is fat excess or fat loss (lipoatrophy).

Numerous studies and anecdotal reports have shown that human growth hormone (Serostim) often effectively shrinks big bellies, buffalo humps and lipomas by decreasing the abnormal fat deposits, although full results may not be seen for a period of time. Because many people have a mixture of fat accumulation in some areas of the body and fat loss in others, concerns have been expressed that Serostim's stimulation of fat burning might actually worsen fat loss in the face, arms and legs. However, this has not been reported in the studies done to date. Clearly, it will not return lost fat to the face, arms or legs, but some people have actually reported that it appears to stimulate enough muscle growth for their limbs to look better.

The standard Serostim dose of the past was 6 mg injected daily, but treatment activists have found that lower doses (1-3 mg), taken either daily or every other day, may work just as well and have the advantage of reducing or preventing the drug's possible side effects -- swollen joints, carpal tunnel syndrome (numbness and pain in the wrist and hand) and higher-than-normal blood sugar levels. Although these lower doses, taken daily, are now being studied for lipodystrophy treatment by the manufacturer (Serono, Inc.), Serostim is currently only approved for standard wasting, making coverage of the expensive drug dependent on the PHA and his or her doctor reporting a weight loss of at least 10% -- the justification for a diagnosis of traditional wasting.

Anabolic steroids combined with exercise can help boost "lean tissue," including muscle size, but have not been found to significantly improve the fat loss/accumulation process. In studies done to date, muscle size has increased but there have been no reductions in accumulated fat, and there have been worrisome decreases in HDL cholesterol (the good or healthy kind of cholesterol) in those using the steroids oxymetholone or nandrolone. In those on oxymetholone, there were also troubling increases in liver enzymes, indicating toxicity to the liver.

Studies of exercise alone have generally shown either no benefit in terms of losing accumulated fat associated with lipodystrophy (in one study, four months of serious weight-lifting four times weekly resulted in no fat loss) or only very small improvements (in another study, there was only 2% fat loss after four months of intensive exercise, including both strength-training and aerobics). But exercise does have many other benefits, including boosting cardiovascular fitness, mental well-being and self-esteem.

In some areas of the body, excess fat can be removed via liposuction (of buffalo humps or lipomas) or standard surgery (for breast reduction), though the fat sometimes returns over time, and neither approach is possible in the belly because of high hemorrhage risk.

Research is underway into the possibility that some drugs used to control diabetes (metformin and the glitazone drugs, all of which help improve insulin sensitivity) may prevent or reverse the development of fat accumulation. However, the studies done to date with metformin have been relatively discouraging, with only small or no decreases in visceral fat (the fat deep inside your body) in the abdomen. And it is important to note that metformin also resulted in significant losses in subcutaneous fat (the fat just under the skin), which is a big negative for those who have already lost fat in their face or limbs. Rosiglitazone has not been shown to either decrease abdominal fat or restore lost subcutaneous fat. Anyone considering metformin should be aware that it can cause lactic acidosis, a rare but potentially lethal side effect of nucleoside analogues (nukes). Whether combining multiple agents (metformin and nukes) that have the potential to cause this problem would increase the overall risk of developing lactic acidosis is not clear, but be forewarned of the possibility.

The drugs d4T and AZT (called "thymidine analogues") have been linked to loss of subcutaneous fat, particularly in the face, arms and legs. Switching these drugs, or avoiding them altogether, may help minimize this side effect.


Mitochondrial Toxicity

Preventing body-shape changes will require a better understanding of causes. For now, Dutch researchers theorize that nuke-induced damage to the mitochondria (your cells' energy factories) may contribute to not only lipodystrophy but also to neuropathy, muscle aches (myopathy), pancreatitis (a painful inflammation of the pancreas gland) and lactic acidosis (a potentially lethal build-up of lactic acid in the body). Although the latter is rare, it can be fatal, so experts urge anyone experiencing any of the symptoms that can indicate lactic acidosis to see their doctor immediately. Increased blood lactate can cause a wide range of symptoms including:

  • fatigue
  • nausea
  • vomiting
  • abdominal pain
  • sudden unexplained weight loss
  • shortness of breath or difficulty breathing (respiratory symptoms)
  • neurologic symptoms (including difficulty moving)

Experts urge anyone who appears to be experiencing lactic acidosis to immediately stop antiretroviral therapy.

Although researchers say that much more research is needed to confirm possible ways to counter mitochondrial toxicity, some have suggested that in the meantime it would be reasonable to try the following:

  • antioxidants (vitamin C, vitamin E, carotenoids, selenium, alpha-lipoic acid, co-enzyme Q10 and others)
  • B vitamins
  • the amino acid L-carnitine (or its other form, acetyl-L-carnitine)

In one of the studies, the following combination reversed lactic acidosis when given intravenously twice daily:

  • L-carnitine (1,000 mg) and
  • B-complex vitamins (in the following doses: 100 mg thiamine, 20 mg riboflavin, 100 mg niacinamide, 10 mg pyridoxine and 10 mg dexpanthenol).
For facial restoration (to help fill out sunken cheeks), injections of a synthetic compound of polylactic acid (New-Fill) have worked wonders. The New-Fill procedure requires several injections into each cheek, repeated three to six times (three weeks apart). In one study, 22 out of 26 people said their faces returned to normal. The change in facial appearance usually lasts for around one year to 18 months, after which another treatment is required to maintain the results.

When done by a skilled plastic surgeon, the use of fat injected into areas of lipoatrophy (fat wasting/loss) can also be effective in restoring facial appearance. The initial facial restoration usually requires only one or two treatments, but later treatments will be required to maintain the benefits. The length of time that the facial restoration remains seems to vary between individuals, with results lasting for as short as three months in some and as long as a year or more in others. Some plastic surgeons say that the best overall results might come with a combination of fat and New-Fill injections but there has been little experience with this so far.

Other therapies may also be available -- ask your doctor for a referral to a plastic surgeon. Reconstructive surgery for lipodystrophy is not covered by provincial formularies. Any plastic surgery may result in scarring.




  
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This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.
 
See Also
An HIVer's Guide to Metabolic Complications
TheBody.com's Lipoatrophy Resource Center
More on Lipodystrophy & Metabolic Complications

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