SEPTEMBER 1998

Are protease inhibitors fattening?

 
Increases in blood fat levels are now known to occur during treatment with Protease inhibitors. In addition, in some people, their face, arms, buttocks and legs becomes thinner while their abdomen/stomach gets bigger. Its mechanism is still unknown. Dieting and physical exercising often help improve the situation.
 
Thanks to their efficacy, protease inhibitors have radically changed the outlook for people with HIV infection. Nevertheless, this new side-effect has been recognised as they have been used by more people for a longer period than the initial studies. It is characterized not only by changes in the blood fat levels mentioned above, but sometimes sugars blood levels, and, in up to 30% of people, by changes in their physical appearance. This issue was raised during the recent Geneva conference. It is also the topic of a chapter in the new French guidelines on the treatment of HIV.
 
Some people are getting a paunch
In some people receiving these drugs, the fatty tissues of the face, shoulders, arms, buttocks and legs slim down to the point where veins can be seen through the skin. At the same time, more fat develops under the abdominal muscles. In women, breast size can also increase. More rarely, fat can accumulate in the lower part of the back of the neck (this is what Americans call the "buffalo hemp"). Some of all of these symptoms are collectively called lipodystrophy, meaning abnormal distribution of body fat. According to some researchers, lipodystrophy could affect 30% of treated persons. It can affect people in different ways and does not always correlate with an increase in your body weight. In some people, the additional waist fat can compensate the weight of the fat lost from the face and limbs. Other people just lose fat from the face, limbs and buttocks without gaining any weight aound their waist.
 
Higher blood fat levels
Abnormally high fat levels (cholesterol and triglycerides) over several years can lead to obstruction of your arteries and to cardio-vascular diseases. This risk is increased when several factors exist (e.g. smoking, cardio-vascular problems in the family). However, it is too early to assess the impact of current treatments on possible heart-related problems. Finally, in some rare cases, very high triglycerides levels can expose to a risk of pancreatitis (severe inflammation of the pancreas, a digestive system gland).
 
Sugar and insulin
After a meal, carbohydrates (sugars) contained in food get into the bloodstream. Then, through the effect of insulin, a hormone produced by the pancreas, sugar gets into some specific cells (muscles, liver, fat cells) where it is used as an energy store. In some patients, protease inhibitors seem to alter the entry of sugar into cells. To compensate this, the pancreas produces more insulin. Sugar is then stocked in fatty cells. In summary, the risk is to loose muscle mass and to gain fat. To limit these effects, it is recommended to make a few changes to your diet (see later paragraph). These abnormalities can be detected by a taking a small sample of your blood and testing insulin and sugar levels after swallowing a sugar drink.
 
Why is this happening?
No-one can yet fully explain these recent findings. HIV infection is known to cause various body disturbances anyway, including increased energy expenditure - where you burn up more calories than an HIV- person doing the same activity (this is why it is usually recommended to HIV-positive persons to eat more). Starting an anti-HIV treatment radically changes the body's energy needs, and probably leads to various disturbances. However, recent studies indicate that protease inhibitors (PI) probably play a major role in lipodystrophy, as these problems are seen more in patients taking these drugs. They have been seen with all PI's (Norvir, Crixivan, Invirase, and Viracept) but it is not yet proven whether some drugs are more to blame than others. Could PI's also alter some of the body cells functions ? Several investigators are looking into this.
 
All right. So, what can you do?
Making changes to your diet together with exercise can perhaps help with some of PI-related problems (insulin or blood fat blood glucose abnormalities, increased weight around your waist). However, this requires a regular and sustained program.
 
Changing your diet
It is a good idea to cut down on quickly-absorbed sugars (sweet deserts, sodas, candies) and to completely avoid them between meals. Try eating more fruit and vegetables which are rich in slowly-absorbed sugars (such as lentils, fava beans, peas, beans, etc.) and with cereals (bread, pasta, rice, etc.). This is because, the quicker sugars are assimilated, the higher the amount of insulin produced by the body and the higher the chances of sugar being stored as fat. The other advantages of slowly-absorbed sugars are that they reduce or even suppress the feeling of hunger and, and therefore, the need to snack between meals. Quickly-absorbed sugars on the other hand lead to a sharp rise,
followed by a sharp drop in blood sugar levels, leading to a wanting to eat sugars again. It is a good idea to cut down on fat, particularly from dairy food (butter, cream, etc.), while keeping a balanced diet.
 
Exercise
Regular, light, physical exercise such as cycling, swimming jogging or rowing uses lots of energy, part of which will reduce stored fat. Regular exercise increases the number of blood cells in muscle, which increases their ability to use sugars from the bloodstream: sugars which are "burnt" this way will not turn into fat.
 
Stabilize insulin and sugars
If regular exercise and diet do not bring back insulin and blood sugar levels to normal, some doctors will offer to use metformin (Glucophage, LP 850, Stagid, Glucinan), which is usually used to treat some forms of diabetes. Recent studies have shown that metformin improves the muscles' ability to use sugars, as does exercise.
 
Fat-lowering drugs
Some drugs are used to lower blood fat levels (Zocor, Elisor, Lipanthyl, Lipanor, etc.). They are used to prevent heart (cardio-vascular) disease. Their usefulness in lowering blood fat levels related to treatment with Pis is not yet known. They need to be used with caution because of potential interactions with PIs. This is why some doctors prefer to use drugs which are often less effective but which do not carry the same risks : Mediator decreases triglycerides absorption in the gut and their synthesis in the liver. Maxepa is made up of fat from some high-fat containing fish species : salmon, tuna fish, herring, etc. Eskimos who eat large quantities of these fish have a low incidence of cardio-vascular diseases. Maxepa helps lowering triglycerides levels and improve the bad/good cholesterol ratio. It should be taken during meals.
 
Growth hormone
Growth hormone increases lean body mass (muscle) at the expense of body fat. It has been used with some success in the US in some people with severe lipodystrophy. This very expensive hormone is only available in France to treat children with growth problems. In spite of many requests by AIDS activist groups to set up trials in HIV-positive people, no such trial has been set up so farS
 
Testosterone
Testosterone is a male hormone, which is also found in women (in whom its plays a less important role). People living with HIV often have lower free testosterone blood levels : total testosterone levels, and not just free testosterone, need to be assayed. This hormone plays an important role in the lean body mass/body fat ratio. The opportunity of taking testosterone supplements can be discussed with your doctor.
 
What if all this is not enough ?
Sometimes, physical exercise and a balanced diet are not enough. If your blood tests (blood fats and sugars) are not improving or if your physical appearance worries you to the point where you may not be able to continue to take your anti-HIV treatment, you should talk to your doctor about changing your treatment. Recent data have shown the efficacy of a new class of drugs (Sustiva, Viramune, Rescriptor, see page 10 of this issue of Remaides, and page 26 of Remaides number 28). Some people who have achieved an undetectable viral load using triple therapy have replaced, with their doctors' approval, the protease inhibitor in their combination, with one of these new drugs. After more than 6 months, their viral load remains undetectable. Nevertheless, little is still known about these drugs and the possibility that they may have similar long-term side effects. In addition, changing treatment does not mean that there is no need to keep exercising or watching your diet !
 
Conclusion
These changes in body appearance may have, at first, been seen by doctors as a mere aesthetic problem, of trivial importance compared with the need to save lives. However, if this issue is not managed, it could lead to complications and be an obstacle to treatment adherence. The close link between quality of life and adherence to treatment can never be overstated.
 

Gilles Pernet

 
Slow and fast sugars
Here is a list of food which are high in sugar. The corresponding numbers indicate how quickly they are absorbed in your body, compared with that of glucose (pure sugar). During treatment with a protease inhibitor, slow sugars (those with a low number) should be preferred to fast sugars (with a high number). For instance, whole-wheat bread (index number 42) is preferable to white bread (index number 87). Nevertheless, be cautious with bread from supermarkets which often contain fast sugars (glucose or saccharose).
 
Coca-Cola : 124
Glucose (sugar) : 100
White bread : 87
Potatoes : 70
"Biscottes" (toasted bread) : 70
Fruit juice : 70
Oatmeal : 64
White rice : 53
Pasta : 50
Banana : 48
Whole-wheat bread : 42
Beans : 40
Lentils : 35
Fresh carrots : 32
Dried peas : 28