AIDS Treatment Update, Issue 61-62, January-February 1998
Megan Nicholson

Changes in body fat have emerged as a major side effect of the anti-HIV drugs called protease inhibitors over the last six months. At this stage, researchers and doctors in Australia will confirm little about this phenomenon called lipodystrophy, although ongoing research is expected to produce results soon.

>>What's it look like?

A fat belly and facial wasting are the main features of lipodystrophy. The word itself means a disturbance in the way the body produces, uses and distributes fat.

To date the changes in body fat have not been scientifically and statistically proven to be a result of protease inhibitors, however the HIV Herald spoke to several HIV health professionals who believe that research will soon confirm the numerous anecdotal reports of fat irregularities both here and overseas.

Dannae Brown, dietitian at St Vincents Hospital Sydney, said "The face is usually the first place that lipodystrophy is evident." She said that a person may retain muscle and weight, especially if they work out regularly, while experiencing substantial facial wasting.

In some people, Brown said, their faces look quite drawn and wasted.

"I've seen a lot of patients who are presenting with quite intact immune systems, or replenishment of their immune systems, but with quite evident facial wasting and loss of fat stores in the limbs - that is, their arms and legs. The loss of tissue seems to be predominantly fat versus muscle," Brown said.

HIV specialist, Dr Andrew Carr, described lipodystrophy as follows: "The anecdotes that have been reported include increased fat around the belly. People are saying that they have become obese around the tummy. Some people are saying they have lost fat in one or more places elsewhere in the body and that can be pretty well anywhere else." Arms, legs, face and bum are all common places for people to lose fat.

>>What's happening?

Protease inhibitors are associated with a number of chemical changes in the body. People taking protease inhibitors may have higher levels of sugars and fats in the blood and raised cholesterol levels.

At this stage it is unclear how the changes in the blood relate to the body fat changes.

A recent edition of the American HIV/AIDS newsletter, AIDS Treatments News (issue 277, 15th August 1997), published an interview with an doctor discussing fat, sugar and cholesterol levels and possible long term side effects of protease inhibitors. HIV infection often causes high blood sugars and high triglycerides , however HIV tends to be associated with low cholesterol. The article said that protease inhibitors may cause increased triglycerides, sugars and cholesterol. These changes may be linked to the wasting and fat accumulation seen with lipodystrophy.

High cholesterol, the article said, is associated with hardening of the arteries in the presence of other risk factors such as hypertension, diabetes, obesity and smoking. The article emphasised that high triglycerides, cholesterol and sugar can all be treated, and urged people on protease inhibitors not to panic if they receive elevated blood test results.

A number of doctors the HIV Herald spoke with dismissed the AIDS Treatment News article as preliminary and speculative, and they argued that the implications of the blood results are not clear at this stage.

>>When does it occur?

Anecdotal reports suggest that facial wasting and stomach fat gain appear at some stage during the first twelve months on protease inhibitors.

Dr Julian Gold of the Albion Street Centre in Sydney, described the fat changes as a slow and progressive change. "Minor changes appear at two to three months," he told the HIV Herald. "More significant changes develop at six to nine months. It then seems to reach an equilibrium."

Anecdotal reports suggest that the fat changes are slowly reversed if a person stops taking protease inhibitors.

>>Do all PIs cause lipodystrophy?

At this stage, experts believe that all the protease inhibitors cause lipodystrophy. Research is currently being undertaken to compare the effects on body fat of the individual protease inhibitors, as well as double combinations of protease inhibitors. There is speculation that a double protease combination is more likely to cause lipodystrophy, however there is no published data available at the current time.

>>`Crix belly'

In the United States, lipodystrophy is commonly referred to as `Crix belly' where a majority of people on protease inhibitors are taking indinavir (brand name Crixivan). However, Carr rejected the suggestion that indinavir is the only protease inhibitor to cause these fat changes. "We don't have comprehensive data on all the protease inhibitors because of the prescribing habits, and because a drug like nelfinavir is very new. And don't forget there will be other proteases coming in the next few months. So all we can talk about is what is being widely prescribed at the moment. That's all we'll be able to draw conclusions about."

>>Saquinavir

There is also some debate about whether or not saquinavir causes lipodystrophy. Julian Gold commented: "It seems to be all proteases at this stage. Saquinavir to a lesser extent probably because saquinavir was so badly absorbed at the early dose levels."

However Carr rejected any definitive claims about saquinavir, saying we need to await further research. He said anecdotal experience of people on saquinavir was limited because most people on saquinavir are also on another protease inhibitor. And as Gold mentioned, the low levels of saquinavir reaching infected cells , especially in the early use of this drug, may have mitigated against the development of lipodystrophy.

>>Ritonavir and nelfinavir

As discussed above, all protease inhibitors are thought to cause lipodystrophy. There has been no specific discussion of ritonavir and nelfinavir to date.

>>How people respond

Brown described the diverse ways in which people respond to the development of lipodystrophy. "Some people are so thrilled with how their viral load has come down to undetectable and their CD4 count has risen, they're quite willing to accept it as a side effect," she said. "Others are very self conscious. I've encountered people who won't leave home except to come to the hospital, they are so conscious of the fact that they look wasted."

Inquiries by the HIV Herald suggest that people on protease inhibitors who have experienced these fat changes believe that reductions in viral load and improvements in health justify the ongoing use of protease inhibitors. However, anecdotal reports suggest that some people on protease inhibitors are finding they are faced with the dilemma that a low viral load comes with a body that is seen to be HIV positive, at least within gay community networks. Unusual weight gain and wasting may also damage a person's self-esteem and confidence.

>>Who will get lipodystrophy?

Not everyone on protease inhibitors will develop lipodystrophy, although at this stage no one knows how common lipodystrophy will be. The HIV Herald was given estimates of between "a small proportion" and "50 percent" of people on protease inhibitors developing wasting and excessive stomach fat.

Treatments spokesperson for the National Association of People with AIDS (NAPWA), Peter Canavan, said that at this stage only a few people on combination therapy are experiencing these fat changes. "Reports are surfacing of a small proportion of people experiencing body changes after going on protease inhibitors," Canavan said. "Anecdotes suggest it affects people with lower CD4 counts to a greater extent."

Dr Andrew Carr cautiously told the HIV Herald: "I don't think it's going to be everybody, nor do I think it's going to be rare." He said that the fat changes were not detected earlier because trials of protease inhibitors were done among people with advanced HIV and that wasting and body changes observed during those trials were attributed to the virus. However, over the last year, many people have commenced early treatment with combination therapy to prevent or delay damage to their immune systems, and the wasting and fat changes caused by protease inhibitors have emerged.

Julian Gold believes that lipodystrophy is an important side effect which is very common. "Most patients have some degree of lipodystrophy which ranges from minor central abdominal swelling to a `pregnant' or 'pot' belly. In people who had no sign of HIV symptoms, it can be very distressing."

>>Caution and panic - Implications for combination therapy

Community organisations and medical professionals clearly do not want to overstate the commonality or implications of lipodystrophy when so little is known. As Professor David Cooper from St Vincent's in Sydney said, "No serious side effects have been observed as a result of these fat changes at this stage. No-one has died as a result of lipodystrophy. The benefits of protease inhibitors is that we know that they save lives."

As Cooper said, protease inhibitors save lives. Certainly many people on combination therapy are living longer and enjoying improved quality of life. Canavan also emphasised the benefits of protease inhibitors: "Many people have gained a new lease on life from the inclusion of protease inhibitors in their combination therapy." He said that anecdotal reports about lipodystrophy should not deter people from combination therapy. "At this stage, we don't have enough information about lipodystrophy to be making definitive statements."

A combination which includes one or two protease inhibitors is the most effective way of reducing HIV in the blood (viral load). If you are expe riencing lipodystrophy, be aware that stopping your protease inhibitor could mean that protease inhibitors may not be as effective for you in the future.

The implications of lipodystrophy for the widespread use of proteases in combination is unclear. If lipodystrophy proves to be relatively common, the appeal of protease inhibitors, especially in early HIV disease, may be reduced.

In addition to the impact of lipodystrophy on size, shape and self image, the health consequences of the changes in fat, cholesterol and sugar levels are unknown.

The HIV Herald found many people reluctant to discuss lipodystrophy, fearing a public discussion will deter people from taking combination therapy. Gold admitted the significance of the side effect. "It's a problem," he told the HIV Herald. "It may have implications for the long term use of protease inhibitors unless some way of reversing the effect can be found," he said.

The need for open discussion of lipodystrophy and further research was emphasised by Canavan. "Community organisations have a responsibility to tell people about all HIV medications and their side effects, and to pass on information about likely drug interactions, as long as that information is correct and in context," he said. Canavan said that lipodystrophy was a major issue. "It is obviously distressing for people experiencing facial wasting and fat stomachs," he said. "However, more research is needed to determine the short and longterm effects on people's health."

>>Treatment and diet

Doctors emphasised that the process which produces the wasting and fat redistribution is not understood, so there is no current remedy to this side effect of protease inhibitors. As Carr said, "We're in the process of trying to think about what to do. The data we have collected so far is just about observing something, so we can sit down and think about how best to manage it. There are clearly options about diet, treatments and stopping proteases and all those issues are going to be raised."

Brown described the ways in which she has attempted to reverse lipodystrophy: "My main line of treatment has been trying to maintain muscle mass. I've had a few people on an anabolic steroid called deca-durabolin in an attempt to maintain or increase muscle mass. It's worked fine for the muscle mass, but it's still not improving the weight loss in the face. People have still lost weight in their legs and their arms. That line of attack certainly helps prevent muscle wasting in a majority of cases but it's not having any effect on the lipodystrophy.

"I've tried a few things - extra hydration, extra carbohydrate and protein intake, extra energy intake. So far, nothing seems to make a difference." Consequently, St Vincents Hospital Sydney, is considering research to assess the effect of specific nutrients and diet variations on lipodystrophy.

Asked if there is anything a person can do with their diet to alter the lipodystrophy, Brown said: "At the moment I can't say a hundred percent. It's unsure whether making dietary modifications are going to make any difference whatsoever. If the fat changes are marked and distressing to the individual, I would suggest that they discuss it with their doctor. Maybe they can get involved in the research, which is trying to understand what is happening." Exercise may also be considered as a way of maintaining muscle, although it won't stop the loss of fat tissue, Brown said.

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