|
Published in the
Bulletin of Experimental Treatments for AIDS January 1999 issue,
by the San Francisco AIDS Foundation.
January
1999 Table of Contents
Main Page
beta@sfaf.org
|
|
Policy Issues Related
to New Metabolic Abnormalities in HIV Disease
Ronald Baker, PhD
The
New Syndrome
There are increasing reports of an emerging new syndrome among people with HIV disease
characterized by serious metabolic abnormalities. As reported in this issue of BETA
(see "Body Fat Changes: More than Lipodystrophy,")
and elsewhere, physical symptoms include a loss of fat in the arms, legs, buttocks, and
face (peripheral wasting), and an accumulation of fat in the abdomen ("protease
paunch"), breasts, and back of the neck ("buffalo hump"). Other
manifestations that may be associated with the syndrome include insulin resistance
(sometimes with diabetes) and elevated blood lipid (fat) levels. The syndrome has been
variously referred to as "peripheral lipodystrophy," "body fat
redistribution," and "metabolic dysregulation."
Direction of Research
There is growing recognition of the need for more research on this new syndrome.
Unfortunately, there is little agreement as to how to prioritize research or how to pay
for it. The pharmaceutical industry is resisting any acknowledgement that the syndrome may
be directly related to anti-HIV drug treatment. In fact, no one yet knows the exact cause
of these metabolic abnormalities. However, the weight of the available evidence suggests a
connection to anti-HIV drug treatment, especially protease inhibitor therapy. Perhaps the
most urgent research objective is to design and implement studies on the cause(s) of
metabolic abnormalities. Development of a consensus case definition of the syndrome is
also of primary importance, so that study results can be compared.
Although preliminary efforts are underway to understand the syndrome better, there is a
bewildering lack of urgency on the part of industry and the government for moving the
appropriate research forward quickly and decisively. Australian researchers led by Andrew
Carr, MD, and David Cooper, MD, have described a hypothetical mechanism for the syndrome
that could explain most of the observed effects, but the group’s ideas require
validation.
An October 1998 meeting organized by the Forum for Collaborative HIV Research in
Washington, DC, concluded that a prevalence study is an important first step in
understanding the syndrome. In addition, the AIDS Clinical Trials Group (ACTG) and the
Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA) are both starting
long-term studies to determine how the syndrome relates to use of protease inhibitors or
non-nucleoside reverse transcriptase inhibitors; however, data from these trials
won’t become available for at least three years.
Experimental Treatment Candidates
HIV community activists, advocates, and people who are experiencing the signs and
symptoms of the new syndrome are clamoring for research into potential treatment for the
associated problems. A few clinicians (most notably Gabriel Torres, MD, in New York City)
have reported some success treating buffalo hump and protease paunch using recombinant
human growth hormone (Serostim). Studies of the effect of growth hormone on body fat are
ongoing. Other therapeutic options worthy of study include lipid-lowering drugs,
anti-diabetes drugs, diet modification, and exercise. Undoubtedly other therapies are also
suitable for study. What appears lacking among the drug companies and in government
circles is the will and determination to implement a variety of treatment studies quickly.
What Can Be Done Now?
Patients and doctors should carefully weigh the benefits and risks of using protease
inhibitors, especially in the case of people who are asymptomatic and at low risk for
immediate disease progression. Protease-sparing regimens may be appropriate for some
people with HIV, although a number of persons with symptoms of body fat redistribution
have never used protease inhibitors. Severe loss of fat in the face and buffalo hump may
be helped by cosmetic surgery, but may recur. However, removal of fat from the abdominal
area through liposuction is dangerous and should not be attempted, due to the possibility
of intestinal perforation or bleeding within the abdominal cavity.
Conflicting Views of the Syndrome’s Importance
Some providers and researchers believe that the syndrome poses no major problems for
people with HIV, and is not widespread enough to warrant serious concern. Combination
therapy using protease inhibitors has resulted in significant improvement in quality of
life, reduction in the incidence of debilitating opportunistic infections, and increased
survival for people with AIDS. This unexplained new syndrome may be a major threat to
these therapeutic advances. Some patients who are experiencing debilitating side effects
have abandoned anti-HIV treatment altogether. Others have decided not to start treatment
out of fear that they will develop disfiguring symptoms. If prevalence rates of the
syndrome are found to approach those reported by Cooper and others (greater than 60% of
protease inhibitor-treated persons), many individuals may decide to discontinue drug
regimens that have served them well. Others who urgently require potent anti-HIV therapy
may refuse it.
Meeting the Challenges
It is imperative that disbelieving providers, researchers, and drug manufacturers
quickly abandon their denial that the syndrome is real. Research on several fronts -- case
definition, prevalence, relation to protease inhibitor therapy, treatment -- must be
adequately funded by government and industry and initiated as soon as possible. Failure to
effectively address these issues in a timely manner threatens to diminish the clinical
successes achieved by widespread use of HAART. Meeting the challenges posed by this
unexpected and distressing phenomenon head-on and with utmost speed is undoubtedly the
best strategy for the long-term benefit of people with HIV, providers, and industry alike.
Ronald Baker is the former Director of Treatment Advocacy at the
San Francisco AIDS Foundation and the former Editor-in-Chief of BETA.
He is currently publisher and editor-in-chief of HIV and Hepatitis.Com,
a new internet publication on treatment for HIV and viral hepatitis
(www.HIVandHepatitis.com).
Page last updated 15 January 1999
|
