POZ IRELAND
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POZ IRELAND
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Page Contents
April 2004
FACIAL WASTING (LIPOATROPHY) Dr John Goode
LIPODYSTROPHY Lipodystrophy: A disturbance of fat metabolism or fat distribution in the body. It is associated with antiretroviral treatment. There is a laying down of visceral fat and a loss of peripheral (arms, legs, face) fat. Until recently, the delay in recognising lipodystrophy meant that many people continued on treatment with worsening symptoms. What are the symptoms? These are the three broad symptoms of lipodystrophy:
Fat gain has been linked to protease inhibitors and fat loss linked to nucleosides. Most researchers still believe that lipodystrophy is the result of several different factors including HIV infection, individual drugs, when treatment was started, family health history, rather than any single cause. Lipodystrophy has been reported in men, women and children from different racial backgrounds. How many people are affected? Studies have found lipodystrophy symptoms are very common in people on treatment – in up to 80% of people. Therefore the current drugs to treat HIV affect the way our bodies process fats and sugar. Over the short-term (1–2 years) most people do not have serious problems, and the benefits from treatment still generally outweigh the risks. However, for a significant minority of people the problems are more serious, or can occur more quickly. It is not possible to predict who will be affected before starting treatment.
Self-reporting and monitoring changes Most people are more sensitive to physical changes in their body than their doctors. There are several ways that you can measure and monitor these changes. MRI and DEXA scans which can look at the breakdown within your body of fat and muscle. Another analysis called BIA (Bio Impedance Analysis) also produces reliable results. Even careful measuring (used in dietetic departments) and photography can make a difference. If you are worried about lipodystrophy, make sure your doctor takes it seriously and offers you some form of monitoring and explains any treatment choices. Changing treatment? Although HIV treatment is linked to lipodystrophy, most of the studies looking at switching individual drugs have not been very helpful. But, just because studies haven’t shown a benefit, doesn’t meant that other treatments would not be better - and whether you decide to change treatment will depend on several things:
Many doctors are reluctant to change a combination that has worked well in terms of viral load and CD4 results, especially if you were previously very ill. However, this may not be appropriate if lipodystrophy has significantly reduced your quality of life. If you change your combination, you have to change to one that is effective against HIV. Switching drugs Studies switching a protease inhibitor in a combination to an NNRTI have generally been too poorly designed to show benefits. There are often reports of better adherence, easier regimens, fewer pills, and most importantly no viral load rebound – but this is not always the case. There have been fewer studies looking at switching nucleosides. If you have alternative drugs to chose from, switching the drug or drugs that you think is causing the problem makes a lot of sense. Test your viral load at least monthly after any treatment change until you can confirm that it is still controlling your HIV. If your viral load rebounds, you can always return to your previous combination immediately, so there is little to lose in at least seeing whether the lipodystrophy will improve. It will be much easier to know if the switch has worked if you have been monitored with a DEXA scan before you make any change. Even if this does not reverse the symptoms, it may stop them getting any worse. Fat accumulation Abdominal fat accumulation associated with lipodystrophy is generally visceral rather than subcutaneous. The main effect of visceral fat is still a change in your appearance, but in severe cases your internal organs can become compressed so that normal functions like breathing and eating can be affected. Buffalo hump is the term given to accumulation of fat across the back of the shoulders and was one of the earliest and most physically distressing symptoms of lipodystrophy to be reported. Treatments include: Many of the investigational drugs used to lower cholesterol and triglyceride are being studied to treat fat accumulation. Steroids (under study) have the potential to reduce fat accumulation but they may worsen symptoms of fat loss. Recombinant Human Growth Hormone (rHGH) showed the potential to reduce visceral abdominal fat and fat pads from the back of the neck and shoulders in several small studies. Benefits have been reported in the short term but fat accumulation reportedly reappears again after the treatment is stopped. Dosing at 3 or 4 mg daily may be more appropriate to minimise side effects. Testosterone cream massaged onto the fat pads has reduced fat pads on the shoulders. A much lower dose would be used for women than for men. (Anecdotal evidence) Removing fat pads using liposuction or surgically have only provided a temporary benefit and are not applicable to abdominal fat. Unless the underlying metabolic mechanism is altered, as with rHGH, fat accumulation has reportedly returned after several months. Fat loss (lipoatrophy) If you loose fat from under the skin on your arms and legs this can make your veins look more prominent. Fat loss from the face is also increasingly common – especially after long-term treatment. This has been linked to nucleoside analogues through mitochondrial toxicity (damage to the energy-producing mechanism in cells) as well as to protease inhibitors, although neither link has been proven. In some studies, d4T has shown a higher risk factor than other nucleosides but these findings have not been consistent. The action of both PIs and nucleosides together may increase the risk for lipoatrophy but lipodystrophy also been reported in HIV-positive people who have not used HIV drugs. Several studies have reported benefits for some people from switching d4T (or AZT) to either abacavir or other combinations of drugs, although there will is a higher risk of viral load rebounding if you have resistance to other HIV drugs. Increasing the number of new drugs may reduce this risk. Any improvements are likely to take at least six months to become noticeable. This is likely to be a more realistic period to reverse changes that took at least this long to develop originally. Injections of polylactic acid (PLA) New-Fill - every two weeks, for eight weeks, have shown promising early results. This approach uses a natural product that does not generate an allergic reaction. Most other approaches try to inject or implant material (fat or silicon) and hope it will stay in position. Very often it either disperses, moves or appears lumpy. PLA works not by replacing fat but by getting your skin to grow thicker – sometimes by up to 1cm. This process continues for months after the injections have finished and there is a lot of interest in updated results from these studies. French HIV treatment guidelines recognise the importance of facial fat loss, by allowing corrective plastic surgery for this to be reimbursed by the French health service. Cholesterol and triglycerides Most clinics test triglycerides and cholesterol levels in your blood every three months at the same time as your CD4 and viral load tests (for all people on therapy) – but you may need to check that this is being done. These tests are best done fasted so don’t have breakfast on blood test days. Although there is a lot of individual variability, fasted triglyceride levels over 4.5 mmol/l is high and over 11.3 mmol/l is very high. There are two types of cholesterol. High Density Lipoprotein (HDL) is a ‘good’ cholesterol – it a larger molecule that removes fats from your arteries. Low Density Lipoprotein (LDL) is a small molecule that carries fats from the liver to other parts of your body and can lead to heart disease. Usually you will have your total cholesterol measured and HDL and LDL checked if this total level is high (i.e. above 6.9 mmol/l). Cholesterol and triglyceride levels can sometimes be improved or controlled by reducing fat and cholesterol in your diet and by starting or increasing exercise. If the underlying cause is related to HIV drugs though, you may need to use additional treatments to lower these levels of fat in your blood. Protease inhibitor-based combinations, particularly if they include ritonavir – indinavir/ritonavir, saquinavir/ritonavir, or lopinavir/r (Kaletra) – are associated with increasing triglyceride and cholesterol levels. Switching the PI to an NNRTI or abacavir has shown beneficial results on blood lipid levels, but there is a slightly higher risk that viral load counts will rebound in people who have already used several nucleoside drugs, so careful monitoring of your viral load is important Other lipid-lowering drugs including gemfibrozil, niacin (nicotinic acid/vitamin B3) and pravastatin need to be used with caution as they may affect the levels of HIV drugs. Studies are also looking at metformin (an insulin sensitising drug), rosiglitazone and growth hormone. A study of HIV-positive men looking at the effects of exercise and testosterone found that testosterone significantly reduced levels of ‘good’ cholesterol (HDL). This is a concern for people with lipodystrophy who already have elevated triglycerides and ‘bad’ cholesterol (LDL). Although muscle gain and fat loss were greater in the testosterone group, levels of good cholesterol increased in people who used exercise without testosterone, and this may be more appropriate for people with lipodystrophy. Blood-sugar levels and diabetes Changes in blood glucose (sugar) levels are also metabolic changes related to lipodystrophy. Glucose levels can be checked by fasting and non-fasting tests. Increases in glucose levels (and diabetes) have been associated with protease inhibitors. A hormone called insulin normally regulates glucose levels in your blood. Increasing levels of insulin stops your liver from increasing levels of glucose. Insulin also allows muscle and other cells to remove excess sugar from the blood. When insulin fails to work in this way, it is called insulin resistance. Although your body produces higher levels of insulin to compensate, if insulin resistance continues to develop, and sugar levels remain high, then you can develop diabetes. When insulin fails to work in this way, it is called insulin resistance. As with HIV-negative people, diet, exercise and stopping smoking help reduce this risk. When this is insufficient, the drugs metformin, rosiglitazone or pioglitazone are being used. Long-term safety of these drugs has not been confirmed in HIV-positive people and the possibility of interactions with other HIV drugs (PIs and NNRTIs) means that they should also be used with caution, and perhaps in conjunction with drug-level monitoring. Women with lipodystrophy may have higher levels of testosterone than either HIV-positive women without lipodystrophy or HIV-negative women. It is not clear whether this is due to high insulin levels associated with lipodystrophy, although a link between the length of time on PI-therapy (but not other drugs) and a greater chance of higher testosterone was found in one study. |
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