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Being Alive
"Protease Paunch" and "Buffalo Hump": Abnormal Fat Redistribution Associated with Protease Inhibitors
Chris Griffin
March 5, 1998
Being Alive 1998 Mar 5: 7

John first became acutely conscious of his enlarged stomach when looking at a photograph someone had taken of him lying on a raft in a swimming pool last summer. His belly seemed to buoy out more than it should. "I was pretty surprised," the former interior decorator says, "because I'd been working out regularly, my diet was relatively conscientious, and I'd just finished participating in the 575-mile California AIDS Ride. Although I'd been pretty sick in 1995, with under 10 T-cells, protease inhibitors had changed all that. I felt I was in terrific shape. But in this photograph I looked downright obese." Despite his improved health, John now joins a growing number of people on protease inhibitor regimens who have reported over the last year a variety of unusual symptoms-unexpected and unaccountable changes in body composition, elevated blood sugar levels (hyperglycemia), new or exacerbated cases of diabetes.

"Protease Paunch" and "Buffalo Hump" Many people on protease inhibitor regimens have been describing enlarged or swollen or distended stomachs. This came to be known at first as "Crix-belly," since so many of the people reporting these symptoms were taking Crixivan (indinavir), but has come to be referred to by the more PI-encompassing "protease paunch." In addition, there have also been reports of large fat deposits appearing in the back area behind the neck (given the unfortunate name "buffalo hump"). Sometimes these symptoms are accompanied by concurrent muscle wasting in the arms, chest and legs, resulting in an exaggerated bulging of veins.

Women are reporting these same symptoms, sometimes accompanied by breast enlargement and the development of a cervical fat pad.

"Despite a gym routine that includes several sets of sit-ups, my stomach now is almost always distended," says John. "When I lie in bed my abdomen feels wider, heavier. This could turn into a real problem for me." After Two Years of HAART John began taking protease inhibitors as soon as they became available, and credits them with saving his life. "I was down to under 10 T-cells, had lost a lot of weight, had experienced several opportunistic infections, and definitely expected to die within the year," he says. "Protease inhibitors changed all that. My T-cell count is now over 200, and I feel great." He started taking saquinavir (Invirase) in January of 1996; in March he switched to ritonavir (Norvir). After tolerating debilitating side effects for seven weeks, he switched again, this time to indinavir (Crixivan). He stayed on Crixivan for nearly nine months, at which point his T-cells began a precipitous drop. He switched yet again, this last August, to nelfinavir (Viracept). While he believes he started gaining this weight while on Crixivan, his switch to Viracept seems to have made it worse.

Not Exclusive to Crixivan Use It is clear now that these abnormalities are not associated exclusively with Crixivan. Six separate reports at the Conference poster session gave accounts of these phenomena, and they were not limited to people on indinavir.

Indeed, all four available protease inhibitors were named in describing these cases. One study found a greater incidence of these abnormalities in people taking a combination of saquinavir and ritonavir, while others reported the greatest incidence associated with Crixivan (which is, admittedly, the most commonly-prescribed protease inhibitor at this time).

By contrast, two of the cases reported upon involved people who had never taken protease inhibitors at all, but had been on other anti-retrovirals, especially d4T.

What is It? Although everyone agrees that antiretroviral therapy seems to be playing a significant role in the development of this syndrome, conversations with doctors at the Conference provided no conclusive understanding of what exactly is causing this redistribution of fat within the body. Indeed, there was debate as to whether or not this tissue is actually fat.

In a report from the National Institutes of Health, Dr. Kirk Miller found that patients typically lose squishy fat beneath their skin, then build up piles of hardened fat elsewhere, which suggested to him a serious chemical change based in the liver.

Another possible explanation offered by Bob Munk writing in Positively Aware is that perhaps normal aging processes have been interrupted by the body's fight with HIV. Once the virus has been controlled by aggressive antiviral therapy, some processes may start making up for lost time, resulting in fairly rapid changes. Or maybe the people experiencing these symptoms have underlying metabolic problems that are somehow triggered by HIV, but don't show up until health improves.

Another theory suggests that the lowering of viral load after long exposure to rapid HIV replication might be responsible for acute changes in the body's metabolism, allowing "the lipids to go crazy" (lipids are one of the principle structural components of living cells). Perhaps the body, after years of feeding upon its own reserves through the course of HIV infection, now, following immune restoration after HAART, tries to "refeed" itself, but in an impaired manner.

A Dense, Fibrous Scar-Like Tissue Dr. Harvey Abrams, a well-known Los Angeles dermatologist with much HIV experience, has performed liposuction on this tissue. "I knew the minute I went in there," says Dr. Abrams, who in his practice performs conventional liposuction daily, "that this was not fat. It's a highly dense, fibrous scar-like tissue, unlike anything I'd seen before." He concurs that this syndrome appears to be related to HAART and renewed immune function. He suspects that it is a "dysfunction in the way the body stores fat," a "derangement in the body's reparative mechanism." The incidence of this fat redistribution syndrome in people taking HAART was estimated by two Conference reports as between 11% and 64%. It seemed to be more common in older patients and those people with a longer exposure to anti-retrovirals.

Case Studies Several people in these case studies experienced very rapid weight gains. One 42-year-old male on a cocktail including Crixivan developed "a pot belly which felt solid," gaining eight pounds in five months. A 26-year-old female gained five pounds in six months; within one month of halting her anti-retroviral therapy, her weight returned to normal and her breast and abdomen enlargement resolved.

Another male, 54 years old, gained 13-15 pounds over six months; though he switched from Crixivan to Viracept, his weight remain unchanged. While the fatty accumulation has been analyzed as "normal adipal (fat) tissue," it is reported to be somewhat more solid and fibrous than usual. Growths have been categorized as "benign lipomas," non-threatening tumors consisting of fat cells.

Surgical Excision and Liposuction A couple of people with "buffalo hump" and the protease belly have had their growths successfully removed surgically or through liposuction. None of the physicians or researchers knew of anything that would reverse "protease paunch," although there was one case of spontaneous remission unassociated with any change in medication or diet, and there was speculation (although no evidence) that this condition might disappear over time.

Changes in diet (to reduce intake of fat and fat-inducing substances) and exercise programs may be effective against this accumulation of fat, but there is no evidence that this is so.

People are cautioned against liposuction, because the procedure can be dangerous. Moreover, with regular liposuction there is a possibility that the weight will return either at the same place or elsewhere in the body. On the other hand, dermatologist Abrams has performed successful liposuction on several cases of "buffalo hump." The procedure is relatively expensive ($2,500-$3,000), and, at least at this time, is not covered by insurance. Dr. Abrams is currently setting up a clinical study of this condition, looking to recruit up to 25 people with "buffalo hump." Participation in this study would not be free-a $900 fee would cover all doctor costs, office visits, lab tests, biopsies, liposuction and follow-up. Dr. Abrams plans to track these participants to see if symptoms recur in the future. Anyone interested should call Dr. Abrams or Mike Frauenheim toll-free at 888.999.5476.

He has also performed liposuction on the abdominal "paunch" in three HIV+ people. After eight months the accumulation of tissue has not returned. (See first-person story below.) Dr. Abrams explains, however, that in order for the tissue-accumulation to be liposuctioned, it must be subcutaneous (just below the skin) as opposed to mesenteric (within the abdominal wall itself, where it will be inoperable, but may respond to diet and exercise).

Foolish and Dangerous: Stopping Meds Some patients were so horrified by their body changes, they took themselves off HAART. Their symptoms, like those of the woman described above, resolved within weeks, but the likelihood that viral activity will rebound is almost certain. This could become a major problem if people refrain from using HAART for fear their bodies will change. One doctor said that he has patients who point to these abnormalities as evidence that we do not know enough about the long-range effects of antivirals and should therefore not take them.

Yet another doctor stated that if "buffalo hump" is the worst of our problems as we live longer and healthier, relatively free from life-threatening opportunistic infections, then we should be happy to live with the disfigurement. Easy for him to say. "One woman last week," said another physician, "told me she was going to stop her therapy, because of the way her stomach looks." These fat-associated phenomena will only add to the already daunting complexities of adherence/compliance that are central to AIDS since the availability of HAART. Clearly further research is desperately needed into these fat abnormalities and their relationship to antiviral therapy.

Dr. Toni Piazza-Hepp of the FDA said his agency has "formally requested that the drug companies" undertake a serious examination of these side effects. So far, only 21 cases have been sent to the FDA for review, but Piazza-Hepp suggested more would come forward.

Liposuction For Protease Paunch: A First Person Report Les is a 42-year-old woman who has been positive nearly 10 years. She began protease inhibitor therapy in 1995 with ritonavir (combined with other antivirals), then Crixivan, then a combination of saquinavir, nelfinavir, d4T and AZT, and now is on Fortovase (soft-gel saquinavir), ddI, hydroxyurea and Viramune. "It seems to be working and I am tolerating it well," she says. Over the last two years or so, I gained a huge belly-as if I were eight months pregnant. In fact, I was asked all the time if I were pregnant. I am normally a very slim, muscular person, a workout fanatic, 5�7_ and about 125 pounds. All fat left my face and butt, and gradually migrated to my belly.

The moment I started reading that others were having this problem too, I went to my doctor (Michael Gottlieb) and said I could not tolerate this and wanted something done immediately.

He agreed that liposuction might be the best solution, because stopping the meds was obviously out of the question. I approached Dr. Harvey Abrams, well known for his work with HIV+ people. I underwent the surgery about four months ago, and am thrilled with the results. I have gained back my flat stomach, and the big belly syndrome hasn't dared rear its fat ugly head since.

An added blessing: my amazing health insurance company has agreed to reimburse me for it! [Editor's note of caution: many insurance companies will not cover this cost, so be careful, don't assume you will be reimbursed, check into it first.] My doctor is pleased because I am pleased, and there were absolutely no complications. I was back to normal activity within a few days, and back to my full-on workout schedule in about a month.

Liposuction worked for me because my "crix belly" was subcutaneous. A bunch of us are manifesting this thing under the abdominal wall-and this I understand is inoperable.

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