“You’re getting a real middle-aged spread there, mate. Too much of the good life, drinking beer and eating rich food?” says this acquaintance, whilst patting my tummy.

Comments about my abdominal girth have been common since I’ve been on HAART compared with the time prior when I had a noticeably skinny frame. Many of my friends with HIV have reported changes in their bodies since being on the drugs – most noticeably losing fat in the arms¹, legs and face (lipoatrophy) and gaining it in the belly², breast (men and women), on the back of the neck (so-called ‘buffalo hump’) and sometimes around the face (‘moon face’).

For some time, medical experts have included fat accumulation along with fat loss as part of the phenomenon of lipodystrophy. In the late 1990s, positive people and physicians described the appearance of large protruding pot bellies as ‘Crix belly’ because it was most noticeably seen in people taking indinavir (Crixivan) at that time. It was later called ‘protease paunch’ because it was thought that it might be a side effect of all or most protease inhibitors.

Past theories

Dr Andrew Carr and colleagues from St Vincent’s Hospital and the National Centre for HIV Epidemiology and Clinical Research (NCHECR) in Sydney were amongst the first researchers in the world to identify these body fat changes and to associate them with HAART. Their early study of patients on HAART in 1997 found 64 percent of their cohort had signs of fat changes (or lipodystrophy), including fat accumulation.

An Australian study in 2000 by Miller, looking at 1348 consecutive patients seen at HIV clinics found 52 percent had peripheral and central fat changes, 37 percent fat wasting only and 11 percent fat accumulation only. European and American studies started to come up with similar statistics. Carr theorised in The Lancet in 1998 that maybe proteases “bind to human proteins, involved in fat metabolism and inhibit their function, leading to inappropriate deposition of fat in some regions of the body.” This theory has never been proven, although some test tube studies by GlaxoSmithKline suggesting, but not proving conclusively, that some proteases may inhibit fat metabolism more than others.

So it came as a shock at the International AIDS Conference in 2002 in Barcelona when the first results of the Fat Redistribution and Metabolism (FRAM) study suggested that HIV-positive people where no more prone to abdominal fat and visceral fat accumulation than the HIV-negative people in the cohort. (There are two types of fat involved here: visceral fat is the fat which deposits around the internal soft tissue of the body such as the stomach or abdomen and subcutaneous fat is the outer layers of fat found on the arms, legs, face, stomach, back and so on).

Drugs not to blame?

The FRAM study compared 425 HIV-positive men (86 percent of whom received antiviral therapy) and a control group of 152 age-matched HIV-negative men from the CARDIA cohort that is evaluating cardiovascular risk in younger men. The data is ‘cross-sectional’ – a snapshot of body fat distribution in study participants at potentially differing parts of their treatment history. The study asked patients and doctors to report on body fat changes and did MRI scanning to accurately measure the amount and distribution of body fat.

FRAM found that the only distinguishing feature of men with HIV infection was fat loss – with 38 percent of the positive cohort reporting subcutaneous lipoatrophy over the past few years compared with 5 percent of the control group. (The drugs most associated with fat loss were d4T and indinavir, but this may reflect the most common drugs available at the time of the study).

Only 40 percent of the HIV-positive individuals reported significant weight gain around the trunk, compared with 56 percent of the controls. HIV-positive people who reported fat loss in their extremities were more likely to report fat loss in their stomachs as well. The authors concluded that visceral fat is not related to HIV or antiviral therapy. Curiously as well, they found that buffalo hump was more common in HIV-negative than HIV-positive men – 12 percent versus 7 percent, although this difference was not statistically significant.

When Professor Carl Grunfeld, the principal investigator of this study and Professor of Medicine at University of California San Francisco, presented his results in Barcelona he knew his findings would be unpopular. He prefaced his presentation with a quote from George Bernard Shaw – “If you are going to tell people the truth make them laugh or they will kill you” – and went on to tell some lame joke.

Judging by the hostile response he received from many in the audience he certainly didn’t amuse, with his findings regarded as controversial, challenging the prevailing beliefs about lipodystrophy at the time. Both positive people and their doctors knew that these tummies were unusual, unlike any weight gain they had experienced in the past. There was an increased prevalence of metabolic problems occurring, with higher cholesterol, triglycerides and insulin resistance – a relationship of these factors to visceral fat deposits seemed likely. And who had ever heard of buffalo humps in HIV-negative people whereas we were seeing these quite commonly in people on HAART?

Age is the strongest determinant of belly fat, according to Grunfeld. “These were men in their middle age. Many had been sick for a decade or so. Then they got treated with decent therapy that reconstituted their immune systems, dropped their viral load and got them healthy again. Along with that they had onset of middle-aged problems,” he said. He acknowledged in a recent article in The New York Times that these paunches appear abnormal but said it was because of the weight loss in the extremities. “It doesn’t look like normal obesity because of the lipoatrophy. You don’t usually see people with thin arms and legs and big bellies.”

Well, is he right or not? Have we been wrong all along when we tell our friends as they pat our tummies, “It’s not my fault, it’s caused by the drugs”? Do we just have normal middleaged spreads? Have the positive people who’ve had to purchase new clothes and bigger belts been imagining these changes? Why have so many positive women on HAART had to increase the size of their bras to accommodate fat changes if the majority is supposed to be losing weight? (The FRAM study data quoted above is only in men and the women’s results are still being processed. Interestingly though a study by the Women’s Interagency Health HIV Study done in major US cities comparing 605 positive women and 210 HIVnegative controls found similar things – the HIV-positive women lost more in the extremities and had similar weight gains to the controls in the belly.)

Carr’s response

I spoke to Dr Andrew Carr for his response to the FRAM research. His first comment was that the HIV-positive cohort weighed less, with the HIV-negative controls being 11 kilograms heavier on average.

“You’ve got the HIV-positive cohort being largely inner urban gay men, 86 percent of whom were taking antiretrovirals, many of whom smoke and are conscious of their weight and others who were injecting drug users (who are often malnourished) compared with largely middleaged white heterosexual men from the suburbs. It’s not an appropriate comparison,” he said.

The FRAM study did not adjust for weight which assumes then that the HIV-positive cohort were the same prior to becoming infected in weight and fat distribution, which is not necessarily the case.

“I think the objective measurement methods used in this trial were fine, but the design and analysis were flawed,” Carr told me. “The two sample groups are not comparable, there is no prospective component to the study [looking at what changes have occurred with these individuals over time], the study hasn’t looked at the relative proportions of fat in the gut and limbs and it certainly hasn’t shown any cause or effect re the fat changes.”

Carr concedes that increased belly fat could be partly to do with ageing, but strongly believes that HIV antiretrovirals contribute as well. “We do see a discernible increase in visceral fat in people who start on protease inhibitors,” he said. “In the first six months we see an increase in visceral fat (up to 10 kg sometimes) and limb fat. The limb fat decreases after that but the visceral fat doesn’t if they remain on proteases.”

An Australian randomised trial called PILLR found five years ago that switching off a protease inhibitor to other drugs lead to reduced visceral fat over six months, Carr points out. “In fact, FRAM found that being on nevirapine protected against visceral fat gain – this shouldn’t be the case if the visceral fat gain is due to ageing,” he said.

The good news is that the number of positive people with distended bellies seems to be falling. Carr says he doesn’t see as many patients with distended bellies as he used to, perhaps because people, particularly those on their first HAART regimen, are more likely to be on non-nucleoside based combinations and avoiding proteases. “Even two years I ago I would have estimated that 50 percent of my patients had increased abdominal girth but now I don’t see it so much.”

There is much discussion of the FRAM study on the web, with all lots of theories about why Grunfeld is right or wrong or his findings premature. It’s been pointed out, for instance, that the study does not say that HIV-positive people don’t gain weight – just that less of them do than the negative controls. The study doesn’t look at how easily it is for both groups to lose the weight once they have it on – a real difficulty for many positive people as those who have tried so hard to get rid of the belly will confirm!

An Australian study by Batterham in 2000 found that it was much harder for positive people on HAART to modify their risk of heart disease and to reduce fat accumulation through dietary changes than for HIV-negative people. Much more needs to be learned about the mechanisms involved with fat re-distribution in the body before we can say that HAART has nothing to do with our bellies, our buffalo humps or other unusual bumps and lumps on our bodies!

What about fat loss?

Lipoatrophy or loss of subcutaneous fat from the arms, legs, face and other parts of the body has been definitely associated with some of the HAART drugs, particularly d4T, AZT and indinavir. John Daye, Health and Treatments Co- Convenor with NAPWA, says though that there could be some hopeful new treatment developments on the way which might help HIV-positive people to reverse some of the wasting caused by antiretrovirals.

“Currently it seems that drugs like d4T and AZT have fat-destructive properties in fat cells. Recent research reported at the Seventh International Workshop on Adverse Drug Reactions and Lipodystrophy in Dublin, Ireland suggests Nucleomaxx, a uridine food supplement, may block some of the harmful effects of nucleoside analogue drugs, leading to fat gain,” he told me.

This research has certainly caused a lot of excitement in the treatments community, although the supplement is expensive and not covered by Medicare or the PBS.

Research into the lipid-lowering drug pravastatin also suggests people on HAART can have fat restored. Further trials need to be done but these are hopeful signs for positive people wanting to regain their former body shape.

Role of exercise?

For people who have these distended bellies, academic arguments about their cause are perhaps less important than finding out how to get their tummies back to normal.

Exercise is one option. A report in the journal Medicine and Science in Sports and Exercise[3] states that progressive resistance training and aerobic exercise has been proven to reduce fat mass from lipodystrophy. This trial on 20 HIV-positive men over 16 weeks (working out three times a week) showed that percentages of trunk fat fell from 54 to 52 percent (an average of 1.1 kg). Not a spectacular result but it does suggest that some loss is possible. Many other similar trials have shown improvements in triglycerides and HDL cholesterol from a combination of these two types of exercise but reductions in trunk fat are not always reported.

Soula Fillipas is an HIV-experienced physiotherapist at the Alfred Hospital in Melbourne. She admits that it can be particularly difficult for those people who have gained a lot of central fat to get rid of it.

“The only way to do it is a combination of diet and exercise. You need aerobic exercise to burn off the fat and abdominal crunches to tone up the stomach muscles. But I highly recommend that people be assessed by an HIV-experienced physiotherapist or trained instructor as it is important to do exercise that is right for your needs.”

“If you have lost lean muscle tissue as part of the HIV wasting process then you shouldn’t risk losing more by doing too much aerobic exercise. Those who have problems with hypertension or high cardiovascular risk factors should do aerobic work but be guided in the amount they do according to their risk and amount of previous muscle loss. Most will gain benefit from resistance exercise, including people with diabetes, for instance. However exercise does not always lead to a loss of central fat. Ageing, along with the medications, plays some role – males in their middle age will often put on weight on their bellies, anyway.

“Some of my patients are doing competitive sports and have no limitations on what they can do at all. Others however have experienced conditions like peripheral neuropathy and cannot do lots of running or high-impact aerobic exercise. Diet can also help with low fat, high-protein foods helping some people to reduce abdominal fat. Patients should also see an experienced dietitian before they start an exercise program.”

Spectacular results

Personal trainer Deanna Blegg, who is HIV-positive herself, uses a six-week program combining diet and exercise that she says has had some spectacular results in helping some positive people on treatments to lose their unwanted fat. “I have found that you can’t control where the fat goes, however you can stop it going there or even make it go away. I run a simple exercise program that has shown success for everyone who’s tried it. One man had a hump on his neck and unsightly fat around his chest and waist. He was constantly getting headaches from the hump pushing his neck forward. The six-week program got rid of the hump, the headaches and 13kg of fat, leaving his arms and legs as they were.

“Under my program men can lose 10-15 kilograms and women 6-10 kilograms of body fat. As a long-term goal though resistance exercise (weight training) helps people to even out their bodies and build up muscle where they have lost it so that areas like the distended tummy are not so noticeable. Alongside an exercise program you need to eat the right sort of foods to develop muscle mass. You are wasting your time if you are going to the gym regularly and not eating the right foods . . . sometimes even doing your body harm.”

I showed Deanna my stomach and she agrees that it is “not a natural thing,” by which of course she means it has been created by medications, not just ageing. “You have a very tight tummy which is clearly being pushed out by some internal aggravation. I believe that anyone who wants to make significant changes to their lumps and bumps can do so with the right education and the right food.”

Well I might have to give it a try – and report back in a future edition. Like a number of positive people in Australia I will probably have to stay on proteases for the foreseeable future with NNRTIs not likely to be effective enough to control my virus. That means having to live with my stomach unless I can find a way to get rid of it.

Have you had a success in removing an obvious ‘protease paunch’ or other fat deposits? Write to Positive Living and let us know how you’ve done it.

Thanks to Dr Andrew Carr, Soula Fillipas and Deanna Blegg for their help with this article.

Footnotes

¹ This is subcutaneous fat or the outer layers of fat on the arms, legs, face etc.

² The fat around the belly is called abdominal or visceral fat accumulation, with deposits around the internal soft tissue of the body such as the stomach or abdomen.

³ Roubenoff et al Volume 31(5) pS125, May 1999