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
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
"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
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
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.
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
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
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
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
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.